1,721,032 research outputs found
Total Synthesis of (+)-Galactostatin. An Illustration of the Utility of the Thiazole-Aldehyde Synthesis
No full textThe natural aza sugar (+)-galactostatin (+)-1 has been prepared from d-serine by sequential installation of chiral 1C and 2C units employing thiazole-based reagents. Thus, the d-serine-derived methyl ester 3 was transformed by 2-thiazolyllithium (4) into the thiazolyl amino ketone 5 which, via syn stereoselective carbonyl reduction and thiazolyl-to-formyl conversion, gave the first key intermediate, the α-hydroxy β-amino aldehyde 10. The olefination of this compound by [(2-thiazolyl)-methylene]triphenylphosphorane (14) followed by osmium tetroxide cis dihydroxylation of the resulting alkene E-16 and cleavage of the thiazole ring produced the second key intermediate, the amino- and hydroxyl-protected 5-deoxy-5-amino-d-galactose 20. The removal of all protecting groups of this compound afforded the target aza sugar (+)-1 in 17.3% overall yield from 3. © 1995, American Chemical Society. All rights reserved
L-nucleosides
No full textThis chapter provides an overview concerning the synthesis of L-nucleosides and their analogues. The first section deals with L-nucleosides, which maintain a close relationship with ribose and deoxyribose derivatives. The second section covers furanose nucleosides without the 2′ and 3′ hydroxyl groups. The third section talks about carbovir, which has been reported as the first carbocyclic nucleoside analogue, with potent anti-HIV activity in vitro; its discovery provided a base for the synthesis of other carbocyclic analogues. Among all types of aza-nucleosides, five-membered pyrrolidine-type nucleosides have been investigated particularly because of their high similarity with naturally occurring nucleosides. Next, the chapter talks about the thionucleosides. Several purine and pyrimidine-L-dioxolane nucleosides have been reported using the acetoxy dioxolane 370 as a glycosyl donor for condensation under classical Vorbrüggen conditions. The final section talks about the oxathiolanyl nucleosides
Synthesis of beta-D-galactosyl ceramide methylene isostere
No full textThe methylene isostere of the glycosphingolipid β-D-galactosyl N- palmitoyl C18 ceramide has been synthesized by a linear reaction sequence starting from a β-linked D-galactopyranosyl aldehyde. First, this sugar aldehyde was converted into a methylenephosphorane which in turn was coupled with N-Boc serinal acetonide. The double bond of the resulting olefin was reduced and the oxazolidine ring was cleaved and oxidized to give a C- glycosyl N-Boc α-amino butanal (three-carbon chain elongation). Then, an additional C15 carbon chain was installed by addition of lithium 1- pentadecyne to the above glycosyl amino aidehyde. The syn/anti ratio (70:30) of the resulting mixture of amino alcohols was reversed (5:95) by an oxidation-reduction sequence to achieve the same stereochemistry as in the hydrophilic head of D-erythro-sphingosines. The major product was subjected to the reduction of the triple bond with LiAlH4 to give the olefin with E geometry. Finally the N-amide group was installed by reaction with palmitoyl chloride and the O-benzyl protective groups of the sugar moiety were removed by treatment with lithium in liquid NH3-THF. The final product was characterized as the O-acetyl derivative
Chelation- and Non-Chelation-Controlled Addition of 2-(Trimethylsilyl)thiazole to a-Amino Aldehydes: Stereoselective Synthesis of the β-Amino-a-hydroxy Aldehyde Intermediate for the Preparation ′ of the Human Immunodeficiency Virus Proteinase Inhibitor Ro 31-8959
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Synthesis of C-2-symmetric dibenzyldiamino diols by double stereoselective Grignard addition to (S,S)-tartraldehyde dinitrone
No full textA new asymmetric two-dimensional synthesis of 1,4-diamino 2,3-diols is illustrated by double addition of benzylmagnesium chloride to the bis- nitrone derived from (R,R)-tartraldehyde and reduction of the resulting dihydroxylamines
Cross-metathesis of C-allyl iminosugars with alkenyl oxazolidines as a key step in the synthesis of C-iminoglycosyl alpha-amino acids. A route to iminosugar containing C-glycopeptides
No full textA general access to a novel class of sugar R-amino acids composed of iminofuranose and
iminopyranose residues anomerically linked to the glycinyl group through an alkyl chain is
described. A set of eight compounds was prepared by the same reaction sequence involving as an
initial step the Grubbs Ru-carbene-catalyzed cross-metathesis (CM) of various N-Cbz-protected
allyl C-iminoglycosides with N-Boc-vinyl- and N-Boc-allyloxazolidine. The isolated yields of the
CM products (mixtures of E- and Z-alkenes) varied in the range 40-70%. Each mixture was
elaborated by first reducing the carbon-carbon double bond using in situ generated diimide and
then unveiling the N-Boc glycinyl group [CH(BocNH)CO2H] by oxidative cleavage of the oxazolidine
ring by the Jones reagent. All amino acids were characterized as their methyl esters. The insertion
of a model C-iminoglycosyl-2-aminopentanoic acid into a tripeptide via sequential carboxylic and
amino group coupling with L-phenylalanine derivatives was carried out as a demonstration of the
potential of these sugar amino acids in designed glycopeptide synthesis
Grignard addition to aldonitrones. Stereochemical aspects and application to the synthesis of C-2-symmetric diamino alcohols and diamino diols
No full textA new example of the stereoselective installation of the amino group at a saturated carbon center via organometallic addition of chiral aldehydes to nitrones is illustrated by the synthesis of 1,3-diamino propanol 1 and 1,4- diamino butandiol 2 units. Three diamino alcohol 1 stereotriads were obtained by stereoselective addition of alkylmagnesium halides (benzyl, cyclohexylmethyl, and metallyl) to the N-benzyl nitrones derived from β- amino-α-hydroxy aldehydes followed by reduction of the resulting N- benzylhydroxylamines. Three 1,4-dibenzyl substituted stereoisomers of type 2 with fixed S configuration at C2 and C3 were prepared by sequential and simultaneous amination in two directions starting from L-threose nitrone and L-tartraldehyde bis-nitrone, respectively. The R,S,S,R isomer obtained by the former route was converted into a seven-membered ring cyclic urea (1,3- diazapin-2-one), i.e., a compound that belongs to a class of nonpeptide HIV- 1 protease inhibitors
Synthesis of taxol and taxotere side chains by 2-(trimethylsilyl)thiazole based homologation of L-phenylglycine
No full textL-Phenylglycine is homologated by the use of 2-(trimethylsilyl)thiazole into (2R,3S)-N-benzoyl- and N-tert-butoxycarbonyl-3-phenylisoserine, which are isolated as acetonide derivatives in 47 and 35% overall yields and with 84 and 90% ee, respectively
A convergent synthesis of the renin inhibitor SPP-100 using a nitrone intermediate
No full textThe total synthesis of SPP-100 and its C-5 epimer involves the construction of the β-amino alcohol segment via addition of the Grignard reagent derived from 3-aryl-2-isopropyl-1-chloropropane to the nitrone functional group installed at C-4 of the pseudoephedrine spiroanellated γ-butyrolactone derivative. © 2001 Elsevier Science Ltd
THIAZOLE-BASED STEREOSELECTIVE ROUTES TO LEUCINE AND PHENYLALANINE HYDROXYETHYLENE DIPEPTIDE ISOSTERE INHIBITORS OF RENIN AND HIV-1 ASPARTIC PROTEASE
No full textA new synthesis of hydroxyethylene dipeptide isosteres for Leu-Leu and Phe-Phe in their y-lactone form la and lb employing β-amino-a-hydroxy aldehydes with singly and doubly protected nitrogen has been developed. These key intermediates, which are available through the thiazole—aldehyde synthesis from L-leucine and L-phenylalanine, weee converted to alkanoates by Wittig olefination and reduction of the ethylenic double bond. Lactonization and stereoselective alkylation at C-2 of the resulting lactones completed the building up of the structural framework. Overall yields weee in the range 16—19% for la and 22—23% for lb. © 1995, American Chemical Society. All rights reserved
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