Open Access Repository of Indian Theses

VERNEKAR, S. P.

STUDIES IN POLYMER STABILISATION : SYNTHESES AND EVALUATION OF STABILISERS-PLASTICISERS FOR POLYMERS (PVC) USING INDIGENOUS RAW MATERIALS

SHET, SHIVARAM

14 
 
SYNOPSIS 
      The thesis entitled “Synthesis and Applications of Pyrrolidine Based Amino acids 
and Hydroxylamine Derivatives” has been divided into three chapters. 
CHAPTER-I: Chapter I describes the Asymmetric synthesis of 3-hydroxyproline: The 
constituent of several bioactive compounds. 
CHAPTER-II: Chapter II is further divided into two sections (Section-A and Section-B). 
Section-A: This section describes the development of a new chiral pyrrolidine-pyrazole 
catalyst for enantioselective Michael addition of carbonyls to nitroolefins and 
Mechanistic insight. 
Section-B: This section describes the development of a new hydroxyphthalimide allied 
triazole-pyrrolidine catalyst for asymmetric Michael additions in water. 
CHAPTER-III: Chapter III is divided into two sections (Section-A and Section-B). 
Section-A: This section describes the application of hydroxylamine derivatives as 
nucleophiles in Ferrier glycosylation: Synthesis of aminoxy pseudoglycals.  
Section-B: This section describes the application of hydroxylamine derivatives in click 
chemistry: Synthesis of novel triazoles and oxime ethers. 
CHAPTER-I 
This chapter describes the synthesis of 3-hydroxyproline: The constituent of several 
bioactive compounds. 
            3-Hydroxyprolines are one of the significant members of -hydroxy--amino 
acids, which are found as key structural components in biologically active compounds. 
Specifically, (2S,3S)-3-hydroxyproline (trans-3-hydroxy-L-proline) 1, was found in 
various pharmaceutically important compounds such as antibiotic Telomycin, 
polyhydroxylated alkaloids,
 
cyclopeptide alkaloids and also serve as valuable chiral 
building block in organic synthesis. It is a natural product first isolated from hydrolysates 
of Mediterranean sponge and later from collagen hydrolysates of various sources. In 
association with our work on synthesis of peptides with unusual amino acids we aimed at 
15 
 
asymmetric synthesis of 1 and its enantiomer employing Sharpless asymmetric 
epoxidation and reductive cyclisation as the key steps. From the retrosynthetic 
perspective, we envisioned (2S,3S)-3-hydroxyproline 1 can be derived from compound 2, 
which could be obtained by reductive cyclisation followed by Boc protection of 
azidoepoxide 3. The azidoepoxide 3 can be attained from a known epoxy alcohol 4, 
which in turn can be easily synthesized from commercially available 3-butyne-1ol 6 
(Scheme 1).  
  
 
 
 
Scheme 1 Retrosynthesis of (2S,3S)-3-hydroxyproline 1. 
 
Synthesis of (2S,3S)-3-hydroxyproline 1: 
            The synthesis of (2S,3S)-3-hydroxyproline 1 was achieved starting from 
commercially available 3-butyne-1-ol 6 as summarized in scheme-2. Accordingly, 6 was 
protected as para-methoxybenzyl ether (PMB) with NaH/PMB-Br in THF and further 
homologated to 7 under EtMgBr/formaldehyde conditions. Compound 7 was reduced 
with LiAlH4 in THF to give allylic alcohol 8 in good yield. Sharpless asymmetric 
epoxidation of 8 with L (+) DET and TBHP afforded the enantiomerically enriched 
epoxide 5 in 72% yield. The tert-butyldimethylsilyl protection of the free hydroxyl group 
of 5 produced compound 9 in 92% yield. The subsequent deprotection of the PMB group 
with DDQ followed by tosylation with TsCl/Et3N in CH2Cl2 resulted in compound 10 (in 
80% yield), which was further subjected to nucleophilic displacement using NaN3 in 
DMF at 70 
0
C to furnish the azidoepoxide 3 in 60% yield. The conversion of compound 6 
to the desired hydroxy pyrrolidine 2 was achieved in a one-pot operation. The reduction 
of azide 3 with Pd/C-H2 in MeOH to amine followed by subsequent epoxide opening (a 
5- endo- tet ring closure)
 
by amine, insitu cyclisation and Boc-protection resulted in the 
16 
 
required hydroxy pyrrolidine 2 in 45% yield. The compound 2 was converted to 1 by tert-
butyldimethylsilyl protection of secondary hydroxyl group followed by selective 
deprotection of primary silylether with HF.Py/THF and subsequent oxidation of primary 
alcohol 11 in to acid 12 using TEMPO/BAIB followed by deprotection of Boc group 
under HCl/EtOH conditions. (Scheme 2) The other enantiomer of 1, (2R,3R)-3-
hydroxyproline ent-1 was synthesized in a procedure analogous to scheme 2, from 8 by 
performing Sharpless asymmetric epoxidation using D (-) DET instead of L (+) DET.  
 
 
 
 
 
 
 
 
 
 
 
 
Scheme 2 Synthesis of (2S,3S)-3-hydroxyproline 1. 
 
           In conclusion, we have achieved the enantioselective synthesis of (2S,3S)-3-
hydroxyproline 1 and (2R,3R)-3-hydroxyproline ent-1 using Sharpless asymmetric 
epoxidation and reductive cyclisation as the key steps. 
 
 
17 
 
CHAPTER-II, Section-A: 
This section describes the development of a new A chiral pyrrolidine-pyrazole 
catalyst for enantioselective Michael addition of carbonyls to nitroolefins and 
Mechanistic insight. 
               Asymmetric Michael addition is one of the widely used basic C-C bond forming 
reactions to test the efficiency of new organocatalysts. Since the discovery of L-proline 
catalysed asymmetric transformations, various proline based organocatalysts have been 
employed for asymmetric Michael reactions with various levels of success. With 
continued our interest in organocatalysis, we have developed a new chiral pyrrolidine-
pyrazole catalyst for asymmetric Michael reaction of carbonyls to nitroolefins. The chiral 
pyrrolidine-pyrazole 1 employed for this work was easily obtained by coupling pyrazole 
with tosylated-L-Boc prolinol 3.  Compound 3 could be easily obtained from L-proline 4 
(Scheme 1 & 2). 
 
 
 
Scheme 1 Retrosynthesis of pyrrolidine-pyrazole catalyst 1. 
  
 
 
 
 
Scheme 2 Synthesis of pyrrolidine-pyrazole catalyst 1.  
18 
 
Evaluation of the catalyst: 
              After the successful synthesis of the organocatalyst 1, initial experiments were 
performed with the reaction between cyclohexanone 8a and nitrostyrene 9a to test the 
efficiency of the catalyst 1. Firstly, the reaction was carried out in CH2Cl2 at room 
temperature by using 10 mol% of catalyst 1. To our delight, the reaction proceeded well 
to give the corresponding Michael adduct 10a in 80% yield with 94:6 (syn\anti) 
diastereoselectivity and 89% enantiomeric excess in 24 h. In order to establish the 
optimized reaction conditions, we have screened a variety of solvents, interestingly the 
best yields (96%) along with high stereoselectivities (syn/anti = 98:2, ee = 94%) were 
observed in the case of solvent-free reaction conditions (for 24 h). After the solvent 
screening experiments, we then examined the effect of various additives and the best result 
was found with TFA (2 mol%), giving the product in 98% yield with (syn/anti = 98:2, ee 
= 95%) in 15 h reaction time.  In addition, we have also tested the effect of catalyst 
loading in the Michael addition of cyclohexanone 8a onto nitroolefin 9a. The decrease in 
catalyst loading had no profound effect on selectivities but took very long reaction times, 
whereas the increase in catalyst loading to 20 mol% produced similar results (Scheme 3).    
 
 
 
Scheme 3 
             Having established the optimal conditions, we then explored the generality of this 
reaction with a variety of nitroolefins 9b-j using cyclohexanone 8a as the Michael donor 
(Scheme 4) (Table 1). The present catalytic system is tolerant to a broad range of 
nitroolefins derived from aromatic aldehydes bearing electron-donating as well as 
electron-withdrawing groups (entries 1 to 6, Table 1) and heteroaromatic aldehydes 
providing a series of γ-nitro carbonyl compounds in high yields with good to high 
selectivities (entries 7 to 9, Table 1). To further expand the scope of the newly prepared 
catalyst, the reaction of β-nitrostyrene 9a with different carbonyl compounds 8b-h has 
also been examined (Scheme 5) (Table 2). 
19 
 
 
 
 
Scheme 4 
             After the above successful experiments we decided to study the mechanistic 
pathway and the transition state involved in the reaction. On the basis of our experimental 
findings, we propose a possible mechanism for asymmetric Michael reaction catalysed by 
pyrrolidine-pyrazole catalyst 1 (Figure 1), which was supported by the ESI-MS of the 
reaction mixture showing peaks at m/z 232 (M+H)
+
 & 381(M)
+
 corresponding to the 
reaction intermediates 11 and 12 respectively. Further, the reaction was also investigated 
by computational studies. 
 
 
 
 
 
 
 
 
 
 
 
Figure 1 Possible reaction mechanism. 
 
20 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
21 
 
 
 
 
Scheme 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
              In conclusion, we have developed a new chiral pyrrolidine-pyrazole catalyst for 
asymmetric Michael reaction of carbonyls to nitroolefins. The reactions were best 
performed with 10 mol% of the catalyst, in combination with TFA under solvent-free 
conditions giving rise to the products in high yields and high stereoselectivities. Further 
the mechanistic insights of the reaction were also demonstrated using mass spectral 
studies and computational studies. 
22 
 
CHAPTER-II, Section-B: 
This section describes the development of a new hydroxyphthalimide allied triazole-
pyrrolidine catalyst for asymmetric Michael additions in water. 
              With our continued interest on organocatalysts,
 
we have developed a new 
hydroxyphthalimide linked triazole-pyrrolidine catalyst 13 from L-proline 4 using the 
Huisgen 1,3- dipolar cycloaddition, „click reaction‟. We envisioned that N-
proporgyloxyphthalimide 14 could participate in a click reaction with Boc-protected 
proline azide 15 to afford Boc protected catalyst, which on deprotection of Boc group 
would yield the desired organocatalyst 13 (Scheme 6 & 7). 
 
 
Scheme 6 Retrosynthesis of organocatalyst 13. 
 
 
 
 
 
Scheme 7 Synthesis of organocatalyst 13. 
 
Evaluation of the catalyst: 
            The efficiency of the catalyst 13 was evaluated in a model reaction of 
cyclohexanone 8a with -nitrostyrene 9a. Initially, the reaction was performed in THF 
with 10 mol% of the catalyst 13 at room temperature and found that the reaction 
proceeded well to give the Michael product 10a in 65% yield, syn/anti = 7:3, ee = 72% 
for 24 h. To further improve the yield as well as stereoselectivity we have investigated 
23 
 
the effect of different solvents  and the best result was observed when H2O was used as 
the solvent (92% yield, syn/anti = 9:1, ee = 88% for 18 h). With the hope of improving 
the yield and selectivity we next examined the effect of various acid additives. From 
these experiments we found that the use of PhCOOH (5 mol%) as an additive improved 
the selectivity as well as the yield (Scheme 8). 
 
 
 
Scheme 8 
             Having the established reaction conditions, a series of nitroolefins 9a-d & 9i-l 
(Michael acceptors) with ketones 8a, 8b & 8f (Michael donors) were examined to expand 
the substrate scope of the catalyst 13 (Scheme 9). All -nitrostyrenes 9a-d & 9i-l 
irrespective of the nature of substituents on aryl group were reacted smoothly with 
cyclohexanone 8a to give the corresponding Michael adducts 10a-d & 10i-l in good 
yields with high diastereoselectivity and enantioselectivity (Table 3). The reaction of -
nitrostyrenes 9a & 9d with cyclopentanone 8a was also equally good resulting in the 
corresponding Michael products 10k & 10r respectively with good yields and 
selectivities (entries 1 and 2, Table 4). Whereas the reaction of -nitrostyrenes 9a & 9b 
with acetone 8f was very sluggish and afforded the desired products 10o & 10s 
respectively in low yield with low selectivity even after prolonged reaction times (entry 3 
and 4, Table 4). 
 
 
 
Scheme 9 
 
 
24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 3 
25 
 
 
 
 
 
 
 
  
 
 
 
Table 4 
            Based on the above experimental results, we propose two potential transition 
states to rationalize the stereochemical outcome of the asymmetric Michael addition 
reaction performed by organocatalyst 13 (Figure 2).   
 
 
 
 
Figure 2 Possible transition states. 
              In conclusion, we have developed a new pyrrolidine-triazole organocatalyst by 
employing click reaction conditions for the asymmetric Michael addition of ketones to 
nitroolefins. The reactions were performed in water with the aid of an acid co-catalyst 
leading to the desired products in good yield and high selectivity.   
26 
 
CHAPTER-III, Section-A: 
This section describes the application of hydroxylamine derivatives as nucleophiles 
in Ferrier glycosylation: Synthesis of aminoxy pseudoglycals. 
               Aminoxy functionality has gained importance in chemistry as well as in 
biology. This functionality was found in many compounds such as carbohydrates, 
peptides, steroids, glycoproteins and also in a large number of biologically active 
molecules.
 
Further the carbohydrates bearing aminoxy group are used as intermediates 
for the synthesis of several bioactive compounds.  These aspects along with our interest 
in Ferrier glycosylation as well as in the exploration of hydroxylamine derivatives, 
prompted us to develop a new method in Ferrier glycosylation by employing 
hydroxylamine derivatives as nucleophiles.   
              Initially the reaction was performed with tri-O-acetyl-D-glucal 1a using N-
hydroxyphthalimide 2a as the nucleophile in dichloromethane at room temperature 
employing Lewis acid catalysts to give the corresponding pseudoglycal 3a in good yields 
and selectivities. Among the catalysts tested, ZnCl2 (2 mol%)  was found to be more 
effective than others in terms of yield, reaction profile and selectivity (Scheme 1). 
  
 
Scheme 1 
   Encouraged by this observation, we performed the Ferrier glycosylation of tri-O-acetyl-
D-glucal 1a using N-hydroxysuccinimide 2b as the nucleophile in dichloromethane at 
room temperature employing ZnCl2 (2 mol%). The reaction proceeded well to give the 
corresponding pseudoglycal 3b in 90% yield with 20:1(α/β) selectivity (Scheme 2). 
    
 
Scheme 2 
27 
 
         With the above successful results, we then explored the scope of this reaction by 
replacing the tri-O-acetyl-D-glucal 1a with other tri-O-protected-D-glucals. In this 
process various tri-O-protected-D-glucals, such as tri-O-benzyl-D-glucal 1b, tri-O-allyl-
D-glucal 1c and tri-O-methyl-D-glucal 1d were reacted independently with N-
hydroxyphthalimide 2a as well as with N-hydroxysuccinimide 2b under the optimized 
reaction conditions and the results of these experiments are summarized in Table 1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 1 
28 
 
              Having developed a useful Ferrier glycosylation, we next examined the 
transformations of the product 3a. Accordingly, the product 3a was subjected to the 
deprotection of phthalimide group using hydrazine hydrate to give the aminoxy 
compound 4 in 65% yield, which was then transformed to 5 and 7 as described in Scheme 
3. The aminoxy compounds 4 and 5 can be used as intermediates for the synthesis of bio-
active compounds. 
 
 
 
 
 
 
 
 
Scheme 3 Transformations from 3a. 
            In conclusion, we have described the use of hydroxylamine derivatives as the 
oxygen atom nucleophiles in Ferrier glycosylation. This transformation, efficiently 
catalyzed by ZnCl2, affords aminoxy pseudoglycal product in good yields and with high 
α-selectivity. The products were also successfully transformed to the useful oxime 
derivatives and may find use in organic synthesis. 
 
CHAPTER-III, Section-B: 
This section describes the application of hydroxylamine derivatives in click 
chemistry: Synthesis of novel triazoles and oxime ethers. 
            Since the discovery of click chemistry, 1,2,3-triazoles have become one of the 
most important heterocycles in medicinal, material and biological research. 1,2,3- 
29 
 
Triazoles have been widely used in synthetic intermediates and industrial applications, 
such as dyes, anticorrosive agents, photo stabilizers, agrochemicals etc. These 
compounds also display numerous biological activities like anti-HIV activity, anti-
microbial activity against Gram positive bacteria, anti-allergic, anti-convulsant, anti-
fungal, β-lactamase inhibitory etc. With our interest in click chemistry as well as in 
exploration of hydroxylamine derivatives we have synthesized several structurally 
divergent 1,4-disubstituted-1,2,3-triazoles 10a-h possessing imido functionality, from N-
propargyloxyphthalimide 8 and different organic azides 9a-h using Huisgen 1,3-dipolar 
cycloaddition „click reaction‟ (Scheme 4) (Figure 1). Further the triazole 10a was 
transformed to aminoxy compound 11, which was used for the synthesis of triazole based 
oxime ethers 12a-l on reaction with various carbonyl compounds (Scheme 5) (Figure 2).  
 
 
  
Scheme 4 
 
Synthesis of triazole based oxime ethers: 
 
 
 
 
Scheme 5 
 
 
 
30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1 Structures of 1,4-disubstituted-1,2,3-triazoles 10a-h. 
 
 
 
 
 
 
31 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2 Structures of triazole based oxime ethers 12a-l. 
 
            In conclusion, we have achieved the synthesis of novel 1,4-disubstituted-1,2,3-
triazoles and triazole based oxime ethers from N-propargyloxyphthalimide and different 
organic azides by employing Huisgen 1,3-dipolar cycloaddition „click reaction‟. 
 
 
 


English

ELECTRICAL AND MAGNETIC PROPERTIES OF SOME BINARY SPINELS

MURTHY, SAHKARHANA

	18	Synopsis




SYNOPSIS
The thesis entitled “Application of the sulfinyl group as a pendant nucleophile in the formal synthesis of (+)-solamin and toward the synthesis of (-)-mucocin” consists of three chapters.
CHAPTER I

Synthesis and applications of enantiommerically enriched sulfoxides in organic synthesis.
This section deals with the preparation of homochiral sulfoxides and the application of the sulfinyl chirality to asymmetric synthesis of bioactive target molecules as reported by various research groups.
CHAPTER II

A formal convergent synthesis of (+)-solamin

           In this chapter a brief account of the synthesis of (+)-solamin reported by various research groups and an elaborate account of the present work is described.
             Solamin is a mono tetrahydrofuran (THF) acetogenin isolated from the seeds of Annona muricata (Annonaceae) along with five other mono THF acetogenins. Acetogenins are a class of compounds that have been isolated from several genera of the plant family Annonaceae. Acetogenins are fairly large molecules, which are characterized by two functional units, the hydroxylated tetrahydrofuran (THF) and the -unsaturated lactone ring, separated by a long alkyl chain. Mccloud et al. reported annonacin as the first annonaceous acetogenin containing a single THF ring. Several other mono tetrahydrofuran acetogenins such as annonacinone, corrosolin, corrosolone, murisolin and solamin have subsequently been isolated. All the reported compounds of this class possess the same basic carbon skeleton, Figure-1. The acetogenins have emerged as a new class of cytotoxic compounds and they are under evaluation as potential anti-cancer agents. Many of these acetogenins have very potent and diverse biological effects such as cytotoxic, anti-tumor, anti-malarial, pesticidal and anti-feedant activities. All the acetogenins were significantly toxic to the two cell lines, from 1 to 10-2 g  ml-1 for VERO and 3 x 10-1 to 10-4 g ml-1 for KB cells.1 Generally mono THF acetogenins are more toxic to KB than VERO cells. The action of the acetogenins in multiple drug resistant cells, mediated by an intracellular glycoprotein pump suggests a possible extracellular action on cell membranes
Figure-1

The retrosynthetic analysis of solamin is depicted in Scheme-1. Solamin 1 was envisioned to be synthesized by alkylation of thio lactone 3 with iodo alkane 2. The iodo compound 2 was envisaged to  be obtained from  the tetrol derivative  4  by a Williamson type reaction. Compound 4 in turn can be obtained by the alkylation of the β-keto sulfoxide 6 with the iodo acetonide 5 and forming C17-C18 bond. The iodo acetonide 5 was envisioned to be obtained by a Pummerer followed by ene reaction from bromo acetonide 7 which inturn can be traced to β-hydroxy sulfoxide 8. The β-keto sulfoxide 6 was similarly traced to β-hydroxy sulfoxide 9 . The β-hydroxy sulfoxides 8 and 9 were envisaged to be readily obtained from      (R)–methyl-p-tolyl sulfoxide. The synthesis of solamin was taken up to showcase the utility of a methodology demonstrating the nucleophilic potential of an inramolecular sulfinyl group to functionalize activated by N-bromosuccinimide to prepare bromohydrins regio and stereoselectively.                                                   


Scheme-1



The key step in the proposed route was the alkylation reaction between the iodide 5 and the β-keto sulfoxide 6 to construct the C17-C18 bond of solamin. Efforts were devoted to identify the optimum conditions using racemic model substrates. The synthesis of racemic iodo compound  16 commenced wih the addition of the lithio anion of racemic methyl p-tolyl-sulfoxide 11  to acrolein 12 to afford an equimolar inseperable mixture of β-hydroxy sulfoxides 13. (For clarity only one of the diastereomer is depicted). Treatment of 13 with a slight excess of  N-iodosuccinimide and H2O in toluene afforded the iodohydrin 14 . Acetylation the iodohydrin 14 using Ac2O and Et3N at room temperature furnished acetate 15. Reduction of sulfoxide to sulfide was carried out using TFAA and NaI in acetone at  0 oC  to yield  iodo sulfide 16. The other partner 18 for the model study was prepared by  treating the lithio anion of 11 with the benzyl ether of (S)-ethyl lactate, Scheme-2.
Scheme-2

Reagents and conditions: a) LDA, THF, 0 oC, 10 min then cooled to -40 oC added 11 30 min, cooled to -78 oC then added 12, 10 min, 80%; b) 1.5 eq NIS, 2 eq H2O, toluene, rt, 30 min, 60%; c) Ac2O, Et3N, DCM, 0 oC to rt, 80%; d) TFAA, NaI, acetone, 0 oC to rt, 70%; e) LDA, THF, 0 oC, 10 min then cooled to -40 oC added 11, 30 min then 17 at 0 oC, 60%; f) m-CPBA, DCM, 0 oC, 10 min, 90%.

The alkylation of 18 with iodo compound 16 was explored under a variety of conditions. Alkylation employing DBU, K2CO3, Cs2CO3 and LDA as bases returned only unreacted starting material. The alkylation was next attempted on the β-keto sulfone 19 obtained by oxidation of 18. Attempted alkylation of 19 with 16 using various bases led to elimination of the acetate group to furnish compound 20, Scheme-3.


Scheme-3

To circumvent the problem of acetate elimination alkylation was attempted on iodo acetonide 21 readily obtained from iodo diol 14. The compound 14 was  treated with 2,2’-DMP in DCM in the presence of catalytic amount of CSA to afford the corresponding acetonide, that on reduction  using  TFAA and NaI in acetone at 0 oC furnished the sulfide acetonide 21. Alkylation of the anoin derived from 19 with 21 did not afford the desired product, a less polar product was isolated and was found to be the allyl alcohol 22, Scheme-4.
A revised synthetic strategy was devised to construct the C17-C18 bond of solamin employing the Wittig –Horner reaction, Scheme-5.

Revised strategy
In the revised strategy, compound 2 was envisaged to be obtained from the enone 37 which in turn was envisioned to be obtained by coupling aldehyde 30 with phosponate 36. The aldehyde 30 can be prepared from bromo acetonide 9 . The phosponate 36 was traced to the oxazolidinone derivative 32 which in turn was to be obtained starting from acid 31, Scheme-5.
Scheme-4


Scheme-5

The synthesis commenced with the addition of the lithio anion of (R)-methyl-p-tolyl sulfoxide 10 to acryloyl imidazole 28 to furnish keto sulfoxide 29. Stereoselective reduction of the ketone to an allyl alcohol using Dibal-H at -78 oC furnished compound 8.Treatment of 8 with a slight excess of freshly recrystallised NBS and water in toluene afforded the bromohydrin 30 which was converted to the corresponding acetonide 7. The acetonide 7 was subjected to Pumerer reaction in the presence of TFAA to afford the intermediate which without isolation on treatment with 1-undecene and SnCl4 furnished the ene product 5. The bromine  in 5 was replaced with the hydroxy group using NaNO2 in DMF at 80 oC to furnish 31. Swern oxidation of the carbinol 31 afforded aldehyde  32, Scheme-6.
Scheme-6

Reagents and conditions: a) LDA, THF, 0 oC, 10 min, 10, -40 oC, 30 min cooled to -78 oC, 28, 30 min 65%; b) Dibal-H, THF, -78 oC, 1h, 75%; c) NBS, H2O, Toluene, rt, 3h, 70%; d) 2,2 DMP, DCM, cat CSA, rt, 4h, 90%; e) TFAA, DCM, 0 oC, 30 min, 1-undecene, SnCl4, 30 min, 60%; f) NaNO2, DMF, 80 oC, 8h, 80%; g) (COCl)2, DMSO, DCM, Et3N, -78 oC,  45 min, 90%. 


The synthesis of the phosponate fragment commenced from the acid 27. Treatment of the oxazolidinone with the mixed anhydride obtained by treatment of acid 27 with pivaloylchloride in DCM/Et3N followed by addition of LiCl  furnished the imide 26. Hydroxylation of the imide using Davis’ reagent and NaHMDS as the base at -78 oC provided the alcohol 33.  Cleavage of the auxillary using   methoxymagnesium bromide yielded  the hydroxy ester 34 which was further protected as its Mom-ether 35. Coupling  of the ester 35 with the anion derived from dimethyl phosponate using n-BuLi at -78 oC afforded the keto phosponate 25, Scheme-7.
Scheme-7

 Reagents and conditions: a) Pivaloyl chloride, DCM, Et3N, 0 oC then oxazolidinone, LiCl, rt, 8h, 90%;  b) NaHMDS, THF, -78 oC, Davis reagent, 15 min, 82%;  c) MeOMgBr, DCM, MeOH, 0 oC, 10 min, 80%; d) MOM-Cl, DCM, Et3N, 0 oC to rt, 10h, 90%;  e) Methyl dimethyl phosponate, n-BuLi, THF, -78 oC, 1h, 75%.

The coupling of the aldehyde 32 and the phosponate 25 was achieved using Ba(OH)2 as the base at room temperature to furnish enone 23. Stereoselective reduction of the enone using Zn(BH4)2 furnished the allyl alcohol 36 (de > 98%). Treatment of the  allylic alcohol 36 with Raney-nickel in a hydrogen atmosphere led to reduction of double bonds and hydrogenolysis of the carbon-sulfur bond. The hydroxyl group was converted to mesylate using methane sulfonyl chloride and Et3N to afford compound 37. Attempted deprotection of the acetonide using aq 70% AcOH to diol instead furnished the cyclized product 38 with concomitant deprotection of the Mom group.

The diol THF derivative 38 was subjected to reaction with TBS-Triflate to afford the diTBS derivative 39 that upon treatment with Pd/C under H2 pressure delivered the debenzylated alcohol 40. This alcohol was converted into the iodo derivative 2, Scheme-8. The compound 2 has been employed as the key intermediate in the synthesis of solamin by Mioskowski and co-workers. Thus a formal synthesis of trans-Solamin was completed.

Scheme-8 
Reagents and conditions: a) Ba(OH)2, aq. THF, rt, 30 min, 70%, b) Zn(BH4)2, THF, -40 oC, 2h, 85%, c) i) Ra-Ni/ EtOH, H2, rt, 2h, 65% ii) Mesyl chloride, DCM, Et3N, 0 oC, 10 min, 100%, d) Aq. 70% AcOH, 80 oC, 4h, 65%, e) TBSOTf, DCM, 2,6-Lutidine, 0 oC, 30 min, 95% f) Pd/C, H2, EtOAc, rt, 6h, 95% g) TPP/I2, Imidazole, THF, 0 oC, 30 min, 71%.




Chapter III
Toward the synthesis of (-)–mucocin.
             In this chapter a brief account of the synthesis of (-)-Mucocin reported by various research groups and an elaborate account of the present work is described. (-)-Mucocin 43, an annonaceous acetogenin, was isolated by McLaughlin and co-workers from the leaves of Rollinia mucosa. Mucocin was the first acetogenin shown to posses tetrahydropyran ring (THP) along with a THF ring. Mucocin shows selective inhibition against A-549 (lung cancer) and PACA-2 (pancreatic cancer) solid tomor cell lines with a potency 10,000 greater than the known antitumor agent adriamycin. The mode of action is through blockage of the mitochondrial complex I (NADH-ubiquinone oxidoreductase) and inhibition of the plasma membrane NADH oxidase resulting in ATP depletion and consequent apoptosis in malignant cells.



The retrosynthetic approach of (-)-mucocin was depicted in Scheme-9. Mucocin 41 was envisaged to be synthesized  from the pyran fragment 42 and the iodo compound 43 employing the boron-alkyl Suzuki reaction to construct the C13-C14 bond. The pyran compound 42 can be obtained from the triene 44 which in turn was envisioned to be obtained by a regioselective opening of epoxy tosylate 48 by diol 47. The vinyl iodide 43 was planned to be synthesized from diol 45 and lactone 3. The diol 45 was envisaged to be obtained from aldehyde 46 using proline 
Scheme-9 
. 
catalysed α-hydroxylation reaction. The  C13-C22 chain of mucocin posseses a C2 symmetry and a bidirectional approach to this fragment was envisioned. The diol fragment 47 was planned to to be prepared from the dibromo compound 49, which in turn can be obtained from the keto sulfoxide 50 that in turn can be obtained from diene diester 52 and (S)-methyl-p-tolyl sulfoxide 51.
The synthesis commenced with the addition of the lithio anion of sulfoxide 51 with diester  52 to furnish the diketo compound 50. The diketo compound 50 on diastereoselective reduction using Dibal-H in the presence of anhydrous ZnCl2  afforded the diol 54 which was too polar and water soluble to isolate from aqueous solution, Scheme-10
Scheme-10
In a revised strategy, Scheme-11, the diene tetrol derivative 47 was envisioned to be obtained via compound 49 from bromohydrin 55. Bromohydrin 55 was envisioned to be obtained from  β-keto sulfoxide 56 which in turn can be obtained from ethyl sorbate 57 and (S)-methyl-p-tolyl sulfoxide 51.







Scheme-11

	












The revised synthesis of tetrol derivative 47 following the revised strategy commenced with the addition of lithio anion of sulfoxide 51 to ethyl sorbate 57 to afford the keto sulfoxide 56. Diastereoselective reduction of the keto carbonyl using Dibal-H in the presence of anhydrous ZnCl2 utilizing the sulfinyl group as the auxillary furnished the dienol 58. The hydroxy group was protected as its silyl ether 59 using TBS-Cl and imidazole. Treatment of  59  with freshly recrystallised NBS (0.95 eq) and water in toluene afforded the bromohydrin 55. Cross metathesis of 55 using Grubbs’ 2nd generation catalyst yielded the dimer 60 in only 50% yield. The yield was significantly improved using Hoveyda-Grubbs catalyst and longer reaction periods to furnish compound 60 in 95% yield. The double bond was reduced using Adam’s catalyst to furnish 49 which was converted to the sulfone 61 using m-CPBA. The sulfone 61 was protected as the dibenzyl ether 62 using benzyl imidate and cat TfOH. The benzyl ether on treatment with an excess of TBAF delivered the allylic alcohol 63 which was desulfonylated using Mg-Hg in ethanol to yield the C2-symmetric diol 47 Scheme-12.

Scheme-12

Reagents and conditions: (a) LDA,THF, -40 oC, 54, 30 min, warm to 0 oC, 60, 52%; b) Dibal-H, ZnCl2,THF, -78 oC, 1h, 82%; c) TBS-Cl, Imidazole, DCM,  0 oC to rt, 8h, 90%; d) NBS, H2O, toluene, rt, 2h, 76%; e)  3 mol% Hoveyda-Grubbs catalyst DCM, reflux, 3 days 95%; f) PtO2, H2, 10 bar, MeOH:PhH (1:1) rt, 12h, 80%; g) mCPBA, DCM, 0 oC to rt, 30 min, 80%; h) Cl3CC=(NH)OBn, cat TfOH, DCM/Cyclohexane, 0 oC to rt, 2h, 70%; i) TBAF, THF,  0 oC to rt, 30 min,  72%; j) Mg, cat HgCl2, EtOH, 0 oC to rt, 2h, 70%.




The synthesis of the epoxy tosylate 48 commenced with the Wittig olefination of the commercially available aldehyde 64 to give the ester 65 which upon alane reduction delivered the allyl alcohol 66. Sharpless asymmetric epoxidation of 66 using (-)-DET furnished the epoxide 67 that upon reaction with tosyl chloride afforded the epoxy tosyltate 48, Scheme-13
Scheme-13


The coupling of the two fragments 47 and 48 was achieved  utilizing  a slightly modified protocol designed by Hoffman in the presence of BF3.Et2O to furnish tosylate 68. Treatment of 68 with K2CO3 in CH3CN and EtOH furnished the epoxide 69. One carbon homologation was performed following Falck’s protocol using trimethyl sulfonium iodide and n-BuLi to afford the allylic alcohol 70. The triene 70 was exposed to Grubbs’ 2nd generation catalyst in refluxing DCM to afford the six membered RCM product 71 and the eight membered RCM product 72 in equal amounts. The structure of these compounds were confirmed by NOESY studies. To improve the formation of 6-membered compound the hydroxy group in 69 was protected as the TES ether 73. This compound was reacted with Me3SI/n-BuLi to afford the triene 74 which was refluxed with Grubbs’ 2nd generation catalyst to yield the pyran 42 as the sole product. Thus the synthesis of C13-C34 fragment of (-)-mucocin was completed, Scheme-14.

Scheme-14 
Reagents and conditions: a) BF3.Et2O, DCM, 0 oC to rt, 15h, 70%; b) K2CO3, EtOH/ AcCN (1:1), rt, 12h, 90%; c) Me3SI, n-BuLi, THF, 0 oC to rt, 1h, 70%; d) 5 mol% Grubbs catalyst IInd generation catalyst, DCM, reflux, 12h, 80%; e) TES-Cl, DCM, Imidazole, 0 oC to rt, 2h, 90%.
The synthesis of the right hand side fragment commenced with the THP ether of propargyl alcohol 75. Alkylation of 75 with octyl iodide 76 using n-BuLi as the base in THF and HMPA as an additive at 0 oC afforded 77. Deprotection of the  THP group in 77 using catalytic CSA in MeOH afforded 78. Isomerisation of 78 to the terminal alkyne using Zipper reaction furnished the alkynol 79. Swern oxidation of 79 yielded the aldehyde 46. 

This aldehyde was subjected to the proline catalysed α-aminoxylation using nitrosobenzene in DMSO followed by insitu reduction with sodium borohydride to yield the aminoxy derivative that was reduced to diol 45 using copper sulfate and MeOH. The diol was alkylated with the lactone 3 using a three step sequence. Initially the primary hydroxy group of the diol was converted to triflate using Tf2O in the presence of 2,6-lutidine and the secondary hydroxy group was converted into the silyl ether using TBS-triflate. This triflate was treated with the enolate generated from 48 using LHMDS at -78 oC to furnish the alkylated product 80. The sulfide group in 80 was converted to the sulfoxide using m-CPBA follwed by thermal elimination to afford the unsaturated lactone 81. The alkyne was converted to the bromo alkyne 82 by treatment with NBS and AgNO3 in acetone. The bromo compound 82 was converted into the vinyl stannane using palladium(0) catalyzed reaction with tributyltin hydride. The vinyl stannane without isolation was directly transformed to vinyl iodide 43 by reaction with iodine. The fragment 43 corresponds to C1-C12 subunit of mucocin, Scheme-15.








Scheme-15
 Reagents and conditions: a) n-BuLi, THF, HMPA, -15 oC to rt, 1h, 65% b) 5 mol% CSA, MeOH, rt, 8h, 90%; c)1,3 Diaminopropane, NAH, 70 oC, 4h, 70%, d) (COCl)2, DMSO, DCM, Et3N, -78 oC, 45 min, 85%; e) i) 20 mol% L-Proline, PhNO, DMSO, rt, 1h; ii) CuSO4, MeOH, rt, 8h, 70% (two steps);  f) Tf2O, DCM, 2,6-lutidine, -78 oC, 10 min then TBSOTf, -78oC to  0 oC, 20 min then added to 48 in LHMDS, THF, HMPA, -78 oC, 30 min, 70%; g) i) m-CPBA/ DCM, 0 oC, 2h; ii) Toluene 80 oC, 6h, 80% (two steps); h) NBS, AgNO3, acetone 0 oC to rt, 1h, 75%; i) Bu3SnH, THF, Pd Cl2 (PPh3)2  0 oC, 1h, I2/ DCM -78 oC, 10 min 70%. 
	
Attempted efforts to couple the trialkyl borane derived from pyran fragment 42 with the vinyl iodide 43 using B-alkyl suzuki reaction using 9-BBN dimer,  PdCl2(dppf)2  and aq.Cs2CO3 as the base were unsuccessful and did not yield the desired product. Efforts are currently in progress to complete the synthesis of (-)-mucocin.
























































ELECTRONIC SPECTRA OF Ni2+ AND V3+ IN CRYSTAL-FIELDS OF D3h SYMMETRY

B., SESHAGIRI RAO

Abstract
Identification and exploration of antibacterial and antibiofilm compounds against different structural targets of Streptococcus pyogenes through in silico and in vitro approaches.
S. pyogenes is a human pathogen capable of causing pharyngitis and strep-throat related infections. Owing to the upsurge of multidrug resistance in S. pyogenes, there is a considerable interest in understanding the pathogenicity of the organism. The first initiative step was to identify proteins that have essential role during survival and regulation of virulence factors in S. pyogenes. The second step is to screen potential antimicrobial compounds against these targets. Due to increased advancement in pharmaceutical sciences, which are yet to be fully explored for therapeutic usage against bacterial pathogens, a large dataset of compounds are available in the public domains. Antibiotics play a crucial part to combat with infectious diseases. Numerous antimicrobial targets are described in the near past to identify lead molecules. In the current study, targets from S. pyogenes that are unexplored are classified into antibacterial and antibiofilm targets. Targets such as SPFabG, SPGyrA, SPGtfs, SPLuxS playing a significant role during survival and pathogenicity of S. pyogenes have been delineated. Screening of the compounds available in the public domains against these targets has culminated in the identification of few potential lead molecules. Therefore, from the in vitro studies, it was confirmed that, these compounds can combat resistance and when fully explored can be used as therapeutic against S. pyogenes related infections. In the current scenario, a user has to necessarily visit all data resources related to the problem in order to get the relevant information. SPEIDS, an annotation database finds utility in the scientific community for a quick view of the collection of data for the inhibitors classified based on various sources and pharmacological actions. Developing database and making it publicly accessible enables a large number of scientists/clinicians to perform further investigation on the drugs essential for their field of research. This classification in SPEIDS will assist the scientific users to choose the ligands for their studies related to S. pyogenes infections.



STUDIES IN THE HIGH TEMPERATURE CHEMICAL REACTIONS INVOLVING A METAL HALIDE - METAL AND METAL HALIDE - METAL OXIDE EQUILIBRIA B CERIUM SULPHIDE (Ce2S3) AND NICKEL CHLORIDE

SHAH, SURESH


AbstractInterface superconductivity and giant proximity effect in La-based cuprate heterostructures The oxide heterostructures and interfaces have gained considerable interest in recent years due to the observation of a number of novel electronic effects like high mobility two-dimensional electron gas, quantum Hall effect, magnetism, and superconductivity. Recent observations of superconductivity at the interface of various cuprate heterostructures is one such phenomena. Deciphering the puzzle of the origin of interface superconductivity may even open a path to enhance the superconducting transition temperature (Tc) of the superconductors. The exciting possibility of using heterostructures to enhance the Tc certainly deserves further investigations. With this enticing prospect, we have studied various new kinds of artificial La-based cuprate heterostructures to explore the existence of interface superconductivity. We have studied various properties of the interfacial superconductor and examined these properties in terms of different theoretical models for two-dimensional superconductors. The academic thrust for understanding the mechanism of high temperature (high-Tc) superconductivity as well as the practical applications of Josephson junction devices have motivated serious experimental and theoretical studies of high-Tc based junctions. Moreover, the mechanism of long range coupling of high-Tc superconductors across a barrier remains an open question to the scientific community. Another objective of this thesis is to perform a careful and systematic study of superconductor-normal metal-superconductor Josephson junctions based on high-Tc cuprate superconductors in order to address the temperature and magnetic field dependence of the supercurrents as well as the long range proximity effect. 




INTERACTIONS INVOLVING ELEMENTARY EXCITATIONS IN FERROMAGNETIC SEMICONDUCTORS

PRADHAN, SHIRISH

Abstract
Investigation on Post-Coital Antifertility Activity of Sapindus trifoliatus Linn. and Pharmacophore Search for Novel Contraceptives.
Considering the worth of developing non-steroidal compounds for better therapeutic management of contraception, the present work has been anticipated to seek rational possibilities in this area through pharmacological approaches and precision based cheminformatics studies. In the experimental section of the project, fruits of an indigenous medicinal herb ‘Ritha’, Sapindus trifoliatus Linn. with documented ethno-therapeutic uses has been explored for its contraceptive properties in rodent model, judging the imminent possibility of herbal resources to play a significant role in healthcare. The aim of the study is to establish the ethnomedicinal uses of the traditional ethno formulation (EF) and the butanol extract (BE) of fruits of the plant scientifically. The results demonstrated that both EF and BE possess prominent post-coital pregnancy interceptive activity through restriction of implantation. Toxicity studies reveal non-toxic nature of the extracts at bioactive dose levels. The extract at dose of 20 mg/kg body weight inhibited fetal implantation (100%), as confirmed by laparotomy on 10th day of pregnancy. The extract also exhibits anti-estrogenic activity in presence of reference hormone and significant variations in gonadal and gonadotrophic hormones in serum. The present findings justify the use of soapnut fruits for pregnancy interception purpose, which may be due to antizygotic, blastocytotoxic or anti-implantation activity. Decreased levels of estrogen and progesterone in test animals may hinder tubal transport of blastocyst and make the uterus unreceptive for implantation. The extract also demonstrated favorable effects on blood-lipid and carbohydrate profiles, suggesting safe nature of the test substance. Phytochemicals abundant in this plant specimen have also been evaluated through models developed in theoretical section of this study. One of the bioactive components, showing promising possibilities through chemometric modeling approach, has been isolated and characterized to be a saponin, -hederin. The contraceptive outcome of this compound asserts that the potency of the extract depends on some other constituents also which might be providing synergistic effect for actual contraceptive activity. On the other hand, bioactive molecules are theoretically modeled through chemometric approaches for deducing active pharmacophore signals, visualizing receptor-ligand interactions and predicting more potent molecules from generated molecular models. Molecules influencing estrogenicity or modulating progesterone receptor binding affinity have been studied extensively. Different physico-chemical, electronic, electro-topological, structural and spatial properties of molecules have been studied and are correlated with biological activity through various statistical approaches to obtain superior quality molecular models. The generated pharmacophore models showed the importance of different biophoric features for selective activities. Finally interaction of ligands at the catalytic cleft of the receptor assisted to envision the requisite pharmacophoric signals. Database screening through these generated mathematical models proposed a few promising compounds which could play prospective role as contraceptive drugs.



THE DIELECTRIC PROPERTIES OF n-LONG CHAIN ALCOHOLS AND THEIR DERIVATIVES

MARATHE, SURENDRANATH

Preface
This thesis describes the study on structure and dynamics of various kinds of
molecular membranes in general. We have studied the morphological transi-
tion of colloidal as well as biologically relevant membranes and qualitatively
argued regarding the interplay between structure and dynamics. Systematic
measurements have been performed to address the issue of ambiguous behav-
ior of molecules under stress when its confined at the interface. The structural
and dynamical effect on interfacial membranes have been studied for soft col-
loidal free standing langmuir monolayer as well as for the quasi two dimen-
sional lipid membranes on solid supports. For organic nanoparticle monolayer
we have observed a correlation between the nanoparticle raft dynamics and the
underlying morphological transition. In this study we have also found a non-
monotonic behavior of dynamical heterogeneity with time which is unusual for
a colloidal system in common and beyond the prediction of Mode Coupling The-
ory. In the case of lipid membrane, we have given an experimental evidence of
lipid molecular rearrangement process at molecular level when its perturbed
by foreign entities. Using sophisticated X-Ray scattering techniques, we were
able to capture the subtle changes happening in the assembly of lipid molecules
in a planar bilayer structure when it interacts with molecules having biological
relevance. In the next level we have used lipid membranes as an active plat-
form to study the physical interaction with several kinds of nanoparticles and
explored the mechanism of active participation of lipid molecules in self assem-
bly process. Besides with the help of Fluorescence Correlation Spectroscopy, we
have also studied the effect of nanoparticles assemblies on the dynamics of lipid
molecules itself.
In Chapter 1, we have provided the background along with a brief review of the
existing literature for understanding the results represented in the subsequent
chapters. This includes discussion on the various physical properties of our sys-
tems of interest, including dynamic behavior of colloidal particles in different
concentration regime and a detailed theoretical understanding regarding the
xv
xvi Preface
glass transition and jamming transition for a highly dense colloidal packing. In
this section we have also discussed the advantages of interfacial microrheology
technique over conventional bulk rheology in terms of efficiency and sensitiv-
ity. Here we have also pointed out the formulation of the multi-particle track-
ing method for achieving different parameters which are correlated in space
and time for a given system. Followed by that the Dynamical Susceptibility
and the anomaly in Van Hove correlation function, for a heterogeneous system
has been argued thoroughly. Towards the end we have discussed about the
general features of another type of two dimensional membrane i.e. the lipid
membrane at interface. Using raft theory we have also tried to give a plausible
explanation of the dynamical heterogeneity of the real cell membrane which
is mimicked by the model supported lipid membrane. Here we have argued
about the structural six fold symmetry of a compact monolayer. Finally in the
last part we have summarized the theoretical aspects of the lipid molecule me-
diated self assembly process and the how the lipid diffusion plays a vital role
in it.
Chapter 2 deals with the aspect of measuring the morphological transition
and its effect on the dynamics for a two dimensional membrane at air/water
interface. It starts with the discussion on the synthesis method for various
types of organic molecule grafted nanoparticles like Cadmium Selenide(CdSe
Quantum Dots) and Gold Nanoparticle(Au NPs) of different size and properties
and followed by a preparation method of 2D film at air/water interface and on
solid substrate using Langmuir-Blodgett method. In this chapter we have dis-
cussed about the basic principles of several experimental tools like Brewster
Angle Microscopy(BAM), Laser Scanning Confocal Microscopy(LSCM), Atomic
Force Microscopy(AFM), Thermogravimetric Analysis(TGA), X Ray Reflectiv-
ity(XRR), Grazing Incidence Diffraction(GID), Fluorescence Correlation Spec-
troscopy(FCS) etc.
Chapter 3 explains the main aspects of the microscopic dynamics in dense
amorphous nanoparticle monolayer at the air-water interface. In this study
we have found a transition in mechanical properties, tracked down through
the systematic variation of isothermal compressibility() with increasing two
dimensional packing fraction of nanoparticle rafts up to the area fraction of
Φ ∼0.82 using Laser Scanning Confocal Microscope. Here we have used multi
Preface xvii
particle tracking method for a close packed gold monolayer with CdSe tracer to
estimate different dynamical properties like Mean Square Displacement(MSD),
Dynamical Heterogeneity etc. These calculations indeed point out the non-
monotonic variation of the amplitude in the four-point dynamic susceptibility
(χ4), a signature of spatio-temporal extension of correlated domains. Along
with that we have also observed the anomaly in trend for the inherent relax-
ation time τ∗ with increasing area fraction(Φ). Interestingly the variation in
χ4 exactly follows the systematic we found for the isothermal compressibility(
) with increasing Φ and that indicates the connection between the observed
macroscopic transitions in mechanical properties and the microscopic dynam-
ical phase transitions. Finally we have given a possible explanation of these
kind of events in terms of the interaction between this sterically stabilized
nanoparticle domains with the help of interpenetration of the capping long
chain polymers of the neighboring nanoparticle.
Chapter 4 opens up the possibilities of probing the hidden features of biomem-
branes at molecular scale with the help of very precise techniques based on
synchrotron X ray diffraction. Here we have studied the rearrangement of the
lipid molecules of an artificial membrane on a solid support as an effect of ad-
sorption of organic branched molecules. In this work we have used non toxic
PETIM dendrimers of two different generations, i.e. G3 and G4 which differs a
lot in terms of size, no of termination groups, molecular weights and protona-
tion states. Our initial measurements shows quantitatively the in- plane and
out of plane symmetry breaking of the lipid bilayer as a result of the interaction
with these two types of molecules. The molecular adsorption effect was quan-
tified in terms of thickness reduction and the change in the scattering length
density(SLD) or the electron density of the top layer in out of plane reflectiv-
ity model. Interestingly both the dendrimers showed different behavior and
the interaction reflected in terms of membrane penetration was found stronger
for higher generation. On the other hand the GID measurement indicates an
enhancement of the in plane unit cell dimension and associated parameters of
the arrangement of lipid molecules as a result of interaction with dendrimers.
The combined XRR and GID measurements indicate a local fluidization of lipid
packing as an outcome of charged branched molecules adsorption on the mem-
brane surface.
xviii Preface
Chapter 5 is summarizes the lipid mediated self assembly process of nanopar-
ticles on a bilayer and how the interaction changes the local properties of the
bilayer represented by the molecular diffusivity. In this study we have used
particles of wide variety of features in terms of size, charge, functionality, po-
larity etc and found a quite dramatic effect in the nanoparticle adsorption event
on a solid supported Lα phased DMPC lipid bilayer. We have also seen that de-
pending on the concentration and amount of surface charge the nanoparticles
form two dimensional regular self assembled patterns on the bilayer surface.
In FCS measurement, we have also found a second group of dynamics ( distri-
bution of diffusivity) along with the normal bilayer diffusion which has been
identified as the diffusion of the lipid molecules where nanoparticles are ad-
sorbed. The inherent increment in diffusivity supports the argument of local
fluidization in lipid membrane in presence of charged nanoparticle as we have
observed in our XRR and GID data described in chapter 4.
Chapter 6 contains the summary and the future perspective of the work pre-
sented here.


PHOTOCONDUCTING PROPERTIES OF THIN FILMS OF LEAD SULFIDE

PHADKE, V.B

ABSTRACT

THEORETICAL AND OBSERVATIONAL ASPECTS OF COSMOLOGICAL INFLATION

This thesis piles up the results of five works in the field of cosmological inflation, inflationary cosmological perturbations, cosmic microwave background (CMB) and weak gravitational lensing of cosmic microwave background.

A simple single field phenomenological model of inflation – the mutated hilltop inflation, has been presented. The presence of infinite number of terms in the Taylor series expansion of the inflation potential makes the mutated hilltop inflation attractive and accurate at the same time.

A brand new way to modify the consistency relation, by taking into account the direct effect of scalar field evolution in estimating observable parameters at the time of horizon exit, has been discussed.

Also, the inflationary cosmological perturbations of quantum mechanical origin have been studied from a different perspective. The complete wave-functions for the inflationary cosmological perturbations (both scalar and tensor) have been derived by solving the associated Schr¨odinger equations. The wave-functions have then been used to derive a cosmological analogue of the Berry phase which may serve as a complementary probe of inflationary cosmology.

With a phenomenological Hubble parameter the quasi-exponential models of inflation have been discussed, using Hamilton-Jacobi formulation. After constraining the model parameter from the theoretical as well as observational ground, we confront quasi-exponential inflation with WMAP–7 data using publicly available code CAMB (Code for Anisotropies in the Microwave Background). The observable parameters are found to fair extremely well with WMAP–7 data.

The analysis also predicts a ratio of the tensor to scalar amplitudes that may even be detected in near future. Finally, weak gravitational lensing in the context of CMB has been discussed. A simple method to extract the unlensed, intrinsic CMB temperature and polarization power spectra from the observed (i.e., lensed) data has been proposed. Using a matrix inversion technique, we demonstrate how one can reconstruct the intrinsic CMB spectra directly from the lensed data.

The delensed spectra obtained by the technique are calibrated against CAMB using WMAP–7 best-fit data and applied to WMAP–9 unbinned data as well. In principle, our methodology may help to subtract the E-mode lensing contribution in order to obtain the intrinsic B-mode power.



STUDIES IN POLYUBSTHANE BASED SYNTHETIC POLYMERS

RANADE, MANJULA A.

The existing dogma of ovarian biology states that a female is endowed with a pre-defined reserve of germ cells and is unable to replenish it during reproductive phase and adulthood. My PhD work showed the presence of two distinct stem cell populations in the ovarian surface epithelium (OSE) of adult mammals (marmoset monkey, rabbit and sheep) including peri-menopausal human ovaries. On the basis of their phenotypic characteristics they were termed as pluripotent very small embryonic-like stem cells and their differentiated or committed progenitors as ovarian germ stem cells. These stem cells upon culture spontaneously differentiate into oocyte-like, parthenote embryo-like, embryoid body-like structures, cells with neuronal-like phenotype and embryonic stem cell-like colonies. Hallmark features of germ cell development typically observed in vivo were also successfully documented during stem cell differentiation into germ cells in vitro. We have proposed a model how neo-oogenesis and primordial follicle (PF) assembly occurs in adult mammalian ovary.The definition of menopause (conventionally known to occur due to depletion of the follicle reserve) can be re-defined in light of our findings. We have detected stem cells even in peri-menopausal human ovary surface epithelium; which is otherwise completely devoid of germ cells and follicles. Thus menopause sets in due to a compromised somatic niche which cannot support the stem cells and their further differentiation.Ovarian cortical tissue culture is conventionally carried out to study various aspects of PF growth and maturation. My work provided evidence that ovarian tissue acts not only as a source of PFs but also as an excellent source of stem cells. Further, the existing concept that PF growth is gonadotropin independent may not indeed be true. My results suggest that Follicle Stimulating Hormone (FSH) exerts action on the ovarian stem cells also.Exploring potential of ovarian stem cells in adult stage and FSH action on the stem cells may open up new avenues for research in the area of oncofertility and in understanding stem cell contribution to ovarian cancers.





ON A MODIFIED COULOMB POTENTIAL AND ELECTRONIC CORRELATION ENERGIES OF SIMPLE ATOMS

RANADE, ANIRUDHA

iPreface
The discipline of dynamical system unifies the language of mathematics
and physics describing its time dependency, evolution and predictability in
all future. The advent of sophisticated instruments and technological devices
completely scrutinize the real world from celestial objects to subatomic parti-
cles and explore some fascinating physics hidden in such a world. The problem
of electromagnetic wave propagation in an ordered magnetic material is an ac-
tive, interdisciplinary area of physics with countless applications ranging from
atomic physics to medical imaging, remote science to signal processing, geo-
sciences to high level data storage devices, cell phones and memory gadgets.
In particular, magnetic storage devices are smart systems, quite appealing and
exploit attractive dynamics through the functional role played by electrons.
Electrons, the fundamental quantum entity intrinsically hold a property called
spin angular momentum or simply spin through which one can obtain all the
information necessary to develop novel magnetic devices. The light-spin inter-
action is inevitable in such a spin based electronic devices and hence inves-
tigation of electromagnetic wave interaction with the spins is the need of the
hour. Though the spin is essentially a quantum entity need more comprehen-
sive knowledge of quantum physics, there exist routes to solve the entire spin
based problem in the classical limit which could be easy for the betterment of
spin studies. The dynamics of such a spin system is governed by the classical
equation of motion designed by Landau and Lifshitz, motivated to model the
interaction of magnetic field with the magnetization developed in the magnetic
medium. Subsequently, people put more effort in this line of studies and came
with more interesting physical consequences, questions and solutions. Soliton
based magnetic studies is one such motivating theory developed and substan-
ii
tial results obtained in the magnetization dynamics that are associated with
solitons. The Landau-Lifshitz equation was later solved for the soliton solu-
tions and the magnetization dynamics in the medium were explained on this
basis of soliton theory. Especially, the nonlinear spin excitations in the form
of solitons made significant in modern physics. Because of its vital importance
and remarkable stability, soliton based magnetization reversal, logic gates, op-
tical soliton to carry information and signal processing are few to list its ap-
plications in recent times. Motivated by the above, this thesis focuses on the
nonlinear magnetization dynamics of ferro/antiferro magnetic material. The-
oretical, analytical and computational studies devoted to the electromagnetic
wave propagation in a ferro/antiferro magnetic medium are well explored and
the nonlinear spin excitations in the medium are governed by soliton modes.
The fundamental dynamical equations governing these systems are the coupled
Landau-Lifshitz and Maxwell’s (LLM) equations. The structure of the thesis as
follows.
Survey of soliton history and its functional role in magnetism, various types
of magnetic material with physically significant spin interactions and its evolu-
tion in the form of solitons are presented in the first chapter of the thesis.
Chapter 2 focus on the solitonic evolution in weak ferromagnet with single
ion uniaxial anisotropy is established through solving the derivative nonlinear
Schro¨dinger (DNLS) equation. The obtained DNLS is rigorously solved by in-
voking tangent hyperbolic function method. Also in the same chapter, as an
extension helimagnetic spin system is solved and the evolution equation is re-
duced to perturbed nonlinear Schro¨dinger (NLS) equation. The NLS equation
is solved for perturbed soliton solution and soliton parameter by employing the
multiple scale perturbation technique.
iii
In chapter 3, spin system comprising site-dependent bilinear, biquadratic
with weak ferromagnetic interaction elevated through Dzyaloshinskii-Moriya
interaction is solved by reducing the coupled LLM to solvable partial differen-
tial equations through reductive perturbation method. A class of soliton spin
excitations is elucidated. In addition magnetization reversal mechanism is also
exploited in these classes of systems.
Chapter 4 is devoted to solve the dynamics associated with the ferromagnetic
spin system with octupole-dipole interaction. The dynamics is completely gov-
erned by perturbed NLS equation and the same is solved for perturbed soliton
solution through the multiple scale perturbation analysis for magnetization re-
versal studies.
Breatherlike electromagnetic wave propagation in a weak antiferromagnet
is completely studied in the framework of LLM equation. The DM interaction
present in the system substantially enhances the amplitude of the soliton and
the individual magnetization exhibit breatherlike spin modes. The above stud-
ies are compiled in fifth chapter of the thesis.
The sixth chapter of the thesis composed of two studies focusing on the
one dimensional nanowire incorporating the weak DM interaction and (2+1) di-
mensional Heisenberg weak ferromagnetic spin chain. Both in nanowire and
(2+1) dimensional spin chain, the equation of motion is governed by nonlinear
Schro¨dinger (NLS) family of equation which is subsequently solved for soliton
spin excitations.


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