1,376 research outputs found
The Conversational Quality of Literature: An Interview with Neel Mukherjee
No full textNeel Mukherjee, author of The Lives of the Others and A State of Freedom talks about his education, his readings, his career as a reviewer and lately as a novelist. He discusses some of the issues brought up by his novels, such as capitalism, the predicament of the have-nots, and literary influences
Supplemental Material - Biomaterial mediated immunomodulation: An interplay of material environment interaction for ameliorating wound regeneration
No full textSupplementary Material for Biomaterial mediated immunomodulation: An interplay of material environment interaction for ameliorating wound regeneration by Krishna Dixit, Hema Bora, Jhansi Lakshmi Parimi, Gayatri Mukherjee, and Santanu Dhara in Journal of Biomaterials Applications.</p
Organocatalytic Cascade Cyclizations for the Enantioselective Synthesis of Spirooxindoles
No full textThe thesis entitled “Organocatalytic Cascade Cyclizations for the Enantioselective Synthesis of Spirooxindoles” is divided into three chapters.
Chapter 1: Catalytic Enantioselective Michael Addition/Cyclization Cascade of
3-Isothiocyanato Oxindoles with Nitroolefins
A myriad of spirocyclic frameworks present in natural product, and pharmaceutically important compounds, has attracted the synthetic organic chemists to explore their preparation in enantioselective manner. Consequently various strategies have been devised for efficiently accessing highly functionalized spirooxindoles. Among these strategies, the use of 3-isothiocyanato oxindoles as the building block appeared as the most popular one. The combination of 3-isothiocyanato oxindoles and a variety of electrophiles have already been reported. However one of the most popular electrophiles, nitroolefins, has never been used in the reaction with 3-isothiocyanato oxindoles. In this chapter, a highly efficient catalytic asymmetric Michael addition/cyclization cascade reaction between 3-isothiocyanato oxindoles and β-substituted nitroolefins with the help of a cinchonidine-derived bifunctional thiourea catalyst has been discussed. Highly functionalized spirooxindoles containing three successive stereocenters were obtained in high yield with moderate to good diastereo- and enantioselectivity. Reference: Kayal, S.; Mukherjee, S. Eur. J. Org. Chem. 2014, 6696-6700.
Chapter 2: Catalytic Aldol-Cyclization Cascade of 3-Isothiocyanato Oxindoles with
α-Ketophosphonates for the Enantioselective Synthesis of β-Amino-α-Hydroxyphosphonates
The oxindole scaffold containing a quaternary stereocenter at the C3 position is a privileged structural motif present in many biologically active molecules and natural products. In this respect, spirooxindoles have received special attention during the past few years. Similarly, β-Amino and/or hydroxy functionalized phosphonic acids and their derivatives are found to display inhibitory activities towards a range of enzymes such as renin, HIV protease, thrombin, and various classes of protein tyrosine kinases and phosphatases. Considering the importance of both oxindole and β-amino-α-hydroxyphosphonic acid, we reasoned that highly functionalized phosphonic acid derivatives based on a spirooxindole framework could be of potential biological significance, if synthesized in enantiopure form This chapter deals with a cascade aldol-cyclization reaction between 3-isothiocyanato oxindoles and α-ketophosphonates for the enantioselective synthesis of spirooxindole-based β-amino-α-hydroxyphosphonate derivatives. Catalyzed by cinchona alkaloid-based bifunctional thiourea derivatives, this protocol delivers 2-thioxooxazolidinyl phosphonates bearing two adjacent quaternary stereogenic centers, generally in high yields with excellent diastereo- and enantioselectivities. Both the product enantiomers are accessible with nearly equally high level of enantioselectivity.
Reference: Kayal, S.; Mukherjee, S. Org. Lett. 2015, 17, 5508-5511.
Chapter 3: Catalytic Michael Addition/Cyclization Cascade of 3-Isothiocyanato Oxindoles with Cyclic α,β-Unsaturated Ketones: A Concise Enantioselective Synthesis of
Bispiro[indoline-3,2'-pyrrolidine]
Among different spirocyclic cores, the spirooxindole framework containing pyrrolidinyl ring represents a very important class owing to their biological activities such as antimicrobial, anticancer, antihypertensive, antidiabetic, antimycobacterial and antitubercular properties.
Similarly, the bispirooxindole scaffold recently has drawn considerable interests because of its exclusive structural and stereochemical diversity. Only a few examples have been reported till date for enantioselective construction of the pharmaceutically important bispirooxindole architectures. Considering the importance of bispirooxindoles and pyrrolidinyl spirooxindole scaffolds, we were interested in merging them in a single molecular framework. In this chapter, a Michael addition/cyclization cascade reaction between 3-isothiocyanato oxindoles and exocyclic enones for the enantioselective synthesis of 3,2′-pyrrolidinyl bispirooxindole derivatives has been illustrated. With the help of a quinine-derived bifunctional squaramide as the catalyst, this protocol delivers bispirooxindoles bearing three contiguous stereogenic centers, in high yields and generally with outstanding diastereo- and enantioselectivity.
Reference: Kayal, S.; Mukherjee, S. manuscript under preparation
Controlling Stereochemistry at the Quaternary Center using Bifunctional (THIO)Urea Catalysis
No full textThe thesis entitled “Controlling Stereochemistry at the Quaternary Center Using Bifunctional (Thio)urea Catalysis” is divided into five chapters.
Chapter 1: Catalytic Enantioselective Construction of Quaternary Stereocenters through Direct Vinylogous Michael Addition of Deconjugated Butenolides to Nitroolefins
The direct use of deconjugated butenolides in asymmetric C–C bond forming reaction is a powerful but challenging task because of the additional problem of regioselectivity along with the issues of diastereo- and enantioselectivity. In this chapter, a direct asymmetric vinylogous Michael addition of deconjugated butenolides to nitroolefins has been demonstrated for the construction of quaternary stereocenter at the γ-position of butenolides. A novel thiourea-based bifunctional organocatalyst, containing two elements of chirality, was synthesized starting from commercially available quinine and (S)-tert-leucine. Remarkably, the sense of stereoinduction in this process is dominated by the tert-leucine segment of the catalyst. Synthetically versatile & highly functionalized γ-butenolides with contiguous quaternary and tertiary stereocenters were synthesized stereoselectively. The reaction was found to be general and a wide range of nitroolefins, with both electron-rich and electron-deficient substituents, underwent smooth reaction under these mild conditions. Similarly, deconjugated butenolides, having various substituents at the γ-position were well tolerated under these reaction conditions and the products were obtained in excellent yields and with uniformly high diastereo- and enantioselectivities.
Reference: Manna, M. S.; Kumar, V.; Mukherjee, S. Chem. Commun. 2012, 48, 5193–5195.
Chapter 2: Catalytic Asymmetric Direct Vinylogous Michael Addition of Deconjugated Butenolides to Maleimides for the Construction of Quaternary Stereogenic Center
In this chapter, a mild and operationally simple protocol for the direct vinylogous Michael addition of deconjugated butenolides to maleimides has been illustrated. Using bifunctional tertiary amino thiourea organocatalyst, derived from a ‘matched’ combination of trans-(1R,2R)-diaminocyclohexane (DACH) and (S)-tert-leucine, the Michael adducts were obtained in excellent yields and with good to high diastereoselectivities and outstanding enantioselectivities. Application of the corresponding diastereomeric catalyst indicated the
dominance of the ‘DACH’ unit over the chiral side chain in determining the sense of stereoinduction. The practicality of this protocol is illustrated by substantial low catalyst loading (down to 5 mol%) and one-pot catalyst recycling. Based on the X-ray structure of the catalyst and observed stereochemistry of the Michael adduct, a stereochemical model is proposed which was further supported by additional experiment.
Reference: Manna, M. S.; Mukherjee, S. Chem.–Eur. J. 2012, 18, 15277–15282.
Chapter 3: Enantioselective Desymmetrization of Cyclopentenedione through Direct Catalytic Vinylogous Michael Addition of Deconjugated Butenolides
Five-membered carbocycles containing one or more stereogenic centers on the ring are privileged structural motifs found in many biologically active natural and non-natural compounds. Among various methods for accessing these enantioenriched carbocyclic frameworks, desymmetrization of prochiral or meso-compounds through catalytic enantioselective transformations represents a powerful strategy. The biggest advantage of such asymmetric desymmetrization reactions lies in their ability in controlling stereochemistry remote from the reaction site. This chapter deals with a highly efficient desymmetrization protocol for 2,2-disubstituted cyclopentene-1,3-diones via direct vinylogous nucleophilic addition of deconjugated butenolides with the help of a tertiary amino thiourea bifunctional catalyst. In contrast to the existing desymmetrization protocols, this method represents a unique example where quaternary stereocenter is generated not only within the ring but also outside the cyclopentane ring. Densely functionalized products are obtained in excellent yields and with outstanding diastereo- and enantioselectivities. The robustness screening indicated that the reaction is highly tolerant to a variety of competing electrophiles and nucleophiles. The remarkable influence of the secondary catalyst site on the enantioselectivity points towards an intriguing mechanistic scenario. To the best of our knowledge, this is the first time such an effect is observed in the context of asymmetric catalysis.
Reference: (1) Manna, M. S.; Mukherjee, S. Chem. Sci. 2014, 5, 1627–1633.
(2) Manna, M. S.; Mukherjee, S. Org. Biomol. Chem. 2015, 13, 18–24. (Perspective)
Chapter 4: Enantioselective Desymmetrization of Cyclopentenediones through Organocatalytic C(sp2)–H Alkylation
Organic compounds are characterized by the presence of various C–H bonds. Functionalization of a specific C–H bond in a molecule with a selected atom or group are among the most straightforward and desirable synthetic transformations in organic chemistry. In this chapter, a simple protocol for the direct alkylation of olefinic C(sp2)–H bond has been developed, not only enantioselectively using an organocatalyst but more importantly without using any directing group. This alkylative desymmetrization of prochiral 2,2-disubstituted cyclopentene-1,3-diones is catalyzed by a dihydroquinine-based bifunctional urea derivative. Using easily accessible, inexpensive and air-stable nitroalkanes as the alkylating agent, this C(sp2)−H alkylation represents a near-ideal desymmetrization and delivers products containing an all-carbon quaternary stereogenic center in good to excellent yields and with high enantioselectivities. The mild reaction conditions allow for the introduction of various functionalized alkyl groups. The possibility of a second alkylation and its applications has also been demonstrated. This protocol is the first example of the use of nitroalkane as the alkyl source in an enantioselective transformation. It is expected that, these findings would have broader consequences and applications to other alkylative and related transformations.
Reference: Manna, M. S.; Mukherjee, S. J. Am. Chem. Soc. 2015, 137, 130–133. (Highlighted in Synform 2015, 67–70)
Chapter 5: Enantioselective Desymmetrization of Cyclopentenediones through Organocatalytic Formal C(sp2)–H Vinylation
The development of catalytic enantioselective C(sp2)–H vinylation reactions remained relatively underexplored for a long time because of various challenges associated with it. As C(sp2)–H functionalization reactions do not generate any stereocenter at the reaction site, development of enantioselective C(sp2)−H functionalization must rely on desymmetrization of prochiral or meso-substrates. More important issue is the identification of a suitable directing group which can efficiently control the regioselectivity during the activation of C(sp2)−H bond. In this chapter, an efficient formal C(sp2)−H vinylation of prochiral 2,2-disubstituted cyclopentene-1,3-dione is developed without using any directing group. This formal C(sp2)−H vinylation of 2,2-disubstituted cyclopentene-1,3-dione is realized using a two-step operation: catalytic enantioselective Michael addition of deconjugated butenolides followed by a base mediated decarboxylation. The vinylated products, containing a remote all-carbon quaternary stereogenic center, are obtained in good yields and with good to high enantioselectivities. Synthetic utility of this protocol is demonstrated by converting the resulting chiral electron-deficient diene into various important building blocks. Significant erosion in enantioselectivity during the decarboxylation process was explained by a plausible mechanism, which was further supported by control experiments.
Reference: Manna, M. S.; Sarkar, R.; Mukherjee, S. manuscript under preparation
Figure_S1 – Supplemental material for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour
No full textSupplemental material, Figure_S1 for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour by Abir Dutta, Kaushik Mukherjee, Venkata Sundeep Seesala, Kaushik Dutta, Ranjan Rashmi Paul, Santanu Dhara and Sanjay Gupta in Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine</p
Enantioselective Carbon-Carbon and Carbon-Heteroatom Bond Formation : From Bifunctional to Anion-Binding Catalysis
No full textThe thesis entitled “Enantioselective Carbon-Carbon and Carbon-Heteroatom Bond Formation: from Bifunctional to Anion-Binding Catalysis” is divided into four chapters.
Chapter 1: Organocatalytic Asymmetric Direct Vinylogous Michael Addition of α,β-Unsaturated γ-Butyrolactam to Nitroolefins
Chiral γ-butyrolactams are privileged structural motifs present in a plethora of natural products as well as pharmaceutically important compounds, such as haplophytine and (+)-lactacystin. They are also been used as a key intermediate for the stereoselective synthesis of anti-influenza drug A-315675. Though the initial works were concentrated over 2-silyloxy pyrroles as nucleophile, the direct use of γ-butyrolactam as nucleophile in enantioselective transformation gained pace during the past decade. Direct use of α,β-unsaturated γ-butyrolactam in vinylogous Michael reaction is not only desirable but also a challenging task due to the need of controlling regio-, diastereo- and enantioselectivity simultaneously. The presence of rather poorly acidic protons at the γ-position of butyrolactam makes the activation via an organocatalyst even more difficult.
In this chapter, the first organocatalytic direct vinylogous Michael reaction of α,β-unsaturated γ-butyrolactam to nitroolefins has been demonstrated. Using quinidine and a simply modified dihydroquinine derivative as the bifunctional catalysts, both the product enantiomers are accessible as single regioisomer (only γ-addition product) and diastereomer with moderate to good enantioselectivity. A range of nitroolefins, bearing aryl, alkyl and heteroaryl substituents were found to be suitable electrophilic partner for this direct vinylogous Michael reaction. We have also successfully utilized α,β-unsaturated moiety of the butyrolactam as a Michael acceptor in a vinylogous Michael/oxa-Michael cascade reaction for the diastereo- and enantioselective synthesis of a tricyclic compound. A plausible mechanistic model is also presented to rationalize the observed stereochemical outcome.
Reference: Ray Choudhury, A.; Mukherjee, S. Org. Biomol. Chem. 2012, 10, 7313-7320.
Chapter 2: A Catalytic Sulfa-Michael Addition/Horner-Wadsworth-Emmons Cascade Reaction for Enantioselective Synthesis of Thiochromenes
Thiochromene derivatives are venerable bioactive molecules having found application as analgesics, anti-cancer, anti-inflammatory and anti-bacterial agents. Although hetero-Michael-initiated cascade reactions involving α,β-unsaturated aldehydes and ketones has been profoundly used for their enantioselective synthesis, similar reactions of the corresponding ester equivalents remained relatively underexplored and almost always require an additional binding site.
In this chapter, a catalytic enantioselective sulfa-Michael addition/Horner-Wadsworth-Emmons olefination cascade is presented. This cascade sequence is initiated by a sulfa-Michael addition to a vinylphosphonate catalyzed by a chiral bifunctional urea derivative and provides an easy access to enantioenriched 2,3-disubstituted thiochromene derivatives. Several aryl and heteroaryl substituted thiochromenes were obtained in excellent yield with high level of enantioselectivity. Our report represents the first example of the use of phosphonate as a traceless binding site in a catalytic asymmetric transformation. The use of a simple catalyst, mild reaction conditions (ambient temperature) and one-pot strategy highlights the benefits of our protocol. Synthetic utility of the products is demonstrated and a model is proposed to rationalize the stereochemical outcome of the reaction.
References: Ray Choudhury, A.; Mukherjee, S. Adv. Synth. Catal. 2013, 355, 1989-1995.
Chapter 3: Organocatalytic Enantioselective Umpolung Vinylation of Cyclic β-Ketoesters
Considering the wide abundance of natural products having vinyl containing quaternary stereocenter, we became interested in an efficient protocol for enantioselective vinylation. We became aware of the fact that all C-H vinylation reported till date couples nucleophile with β-carbon of an electron withdrawing group. However, there is no example of C-H vinylation which couples nucleophile with α-carbon of an electron withdrawing group. Considering the fact that α-carbon of an electron withdrawing group is nucleophilic in nature, such a combination would lead to “mismatched polarity” and render the reaction electronically impossible. Therefore, a reversal of polarity or umpolung reactivity would be necessary for this coupling.
In this chapter, an efficient formal enantioselective umpolung α-vinylation of cyclic β-ketoester by an one-pot two-step sequence is described. This two-step protocol consists of a catalytic enantioselective Michael reaction followed by base mediated nitrous acid elimination. The products, bearing an all-carbon quaternary stereocenter including a vinyl moiety, was synthesized in high yield with excellent er. β-Nitroenones containing substituted aryl or heteroaryl group produced the vinylated product with excellent enantioselectivity. Our protocol demonstrates the first use of β-nitroenones as an electrophilic component in an enantioselective reaction. This is also the first example of a catalytic umpolung vinylation reaction of β-ketoester. The reaction could be scaled up at least to 1.0 mmol scale without hampering the yield or enantioselectivity. A model based on the bifunctional nature of the catalyst was proposed to rationalize the observed stereochemical outcome of the reaction.
References: Ray Choudhury, A.; Manna, M. S.; Mukherjee, S. manuscript under preparation.
Chapter 4: Enantioselective Dearomatization of Isoquinolines by Anion-Binding Catalysis en Route to Cyclic α-Aminophosphonates
α-Aminophosphonates and related α-aminophosphonic acid derivatives are used extensively in medicinal and pharmaceutical sciences as surrogates of α-amino acids. The strong correlation between the biological activities of compounds containing α-aminophosphonic acids and their absolute configuration renders the enantioselective synthesis of α-aminophosphonates imperative to such studies. Considerable advancement has taken place in the catalytic enantioselective synthesis of acyclic α-aminophosphonates using various strategies. In contrast, enantioselective synthesis of cyclic α-aminophosphonates remains elusive, despite their prominent abundance in biologically active molecules.
In this chapter, the development of an enantioselective dearomatization of diversely substituted isoquinolines through acyl activation and nucleophilic addition of silyl phosphites is presented.
Using a simple and easy to prepare tert-leucine derived thiourea as the anion-binding catalyst, this base-free protocol delivers cyclic α-aminophosphonates in excellent yields with moderate to high enantioselectivities. The reaction was found to be general with respect to different isoquinolines when applied to monosubstituted isoquinolines bearing substituent at nearly every position and even to disubstituted isoquinolines. Our protocol was also found to be suitable for dihydroisoquinolines. This is the first example of the use of silyl phosphites as the nucleophile in asymmetric dearomatization reactions driven by anion-binding catalysis. In fact, this is also the first time asymmetric anion-binding catalysis has been applied to the synthesis of α-aminophosphonates. A preliminary experiment with quinoline points toward potential applicability of this strategy to other nitrogenous heteroaromatics.
References: Ray Choudhury, A.; Mukherjee, S. under revision
Figure_S4 – Supplemental material for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour
No full textSupplemental material, Figure_S4 for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour by Abir Dutta, Kaushik Mukherjee, Venkata Sundeep Seesala, Kaushik Dutta, Ranjan Rashmi Paul, Santanu Dhara and Sanjay Gupta in Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine</p
Figure_S2 – Supplemental material for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour
No full textSupplemental material, Figure_S2 for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour by Abir Dutta, Kaushik Mukherjee, Venkata Sundeep Seesala, Kaushik Dutta, Ranjan Rashmi Paul, Santanu Dhara and Sanjay Gupta in Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine</p
Figure_S3 – Supplemental material for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour
No full textSupplemental material, Figure_S3 for Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour by Abir Dutta, Kaushik Mukherjee, Venkata Sundeep Seesala, Kaushik Dutta, Ranjan Rashmi Paul, Santanu Dhara and Sanjay Gupta in Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine</p
Bharati Mukherjee, conquering America
No full textAuthor Bharati Mukherjee discusses her works and what it means to be an Asian immigrant in the United States.Host, Bill Moyers. Director of photography, Eric Camiel ; editor, Michael Collins ; theme music, Michael Bacon
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