Yashwant D. Vankar

Chemistry of glycosphingolipids—carbohydrate molecules of biological significance

The chemistry for the synthesis of glycosphingolipids has been greatly advanced in the last two decades, and now almost any compound of any structural complexity can be prepared. The methodology is based on the development of efficient glycoside bond formation strategies in order to obtain the oligosaccharide moiety, on the synthesis of useful sphingosine intermediates, and finally on their successful ligation in order to provide neutral as well as acidic glycosphingolipids (i.e. gangliosides). Also enzymatic approaches towards this goal have been investigated. Recent conformational and biological studies exhibit a rapidly growing understanding of the physical properties and the importance of glycosphingolipids which is essentially based on the great synthetic achievements discussed in this review.

Synthesis of β-O-glycosides using enol ether and imidate derived leaving groups. Emphasis on the use of nitriles as a solvent☆

Abstract Two new methods of β-glycoside synthesis using donors 2 and 3 that contain leaving groups derived from enol ether and imidates have been developed. Effect of nitriles as a solvent in directing mainly β-glycosidations has been compared with various methods reported in the literature. Effectiveness of leaving group at low temperatures and participation of nitriles in the formation of nitrilium—nitrile conjugate has been emphasized.

Sodium iodide/boron trifluoride etherate: A mild reagent system for the conversion of allylic and benzylic alcohols into corresponding iodides and sulfoxides into sulfides

Abstract A variety of allylic and benzylic alcohols have been converted into the corresponding iodides using NaI/BF3.Et2O. Selective conversion of allylic and benzylic alcohols in preference to primary saturated alcohols has also been demonstrated. Further, the same reagent system has been used to convert sulfoxides into sulfides under mild conditions.

2-Nitroglycals as Powerful Glycosyl Donors: Application in the Synthesis of Biologically Important Molecules

[Reaction: see text]. The biological significance of oligosaccharides and glycoconjugates is profound and wide-ranging. For example, the mucins have attracted attention because of their role in fundamental cellular processes such as fertilization, parasitic infection, inflammation, immune defense, cell growth, and cell-cell adhesion. Increased expression of mucins is implicated in malignant transformation of cells. Antifreeze glycoproteins also are of interest because they are important for the survival of many marine teleost fishes that live in polar and subpolar waters. The synthesis of glycoconjugates requires methods for glycoside bond formation, the most difficult aspect of which is the assembly of monosaccharide building blocks. This Account discusses a valuable addition to the repertoire of methods for glycoconjugate synthesis: an approach that involves 2-nitroglycal concatenation. For a long time, methods for glycosylation via glycosyl donor generation required either an anomeric oxygen exchange reaction or anomeric oxygen retention. In the case of an anomeric oxygen exchange reaction, activation of the glycosyl donors demands a promoter in at least equimolar amounts. However, anomeric oxygen retention, such as base-catalyzed formation of O-glycosyl trichloroacetimidates, can be activated by catalytic amounts of acid or Lewis acid. Alternatively, glycals, which are readily available from sugars, can be an attractive starting material for glycoside bond formation. Their nucleophilic character at C-2 permits reactions with oxygen, nitrogen, and sulfur electrophiles that under high substrate stereocontrol generally lead to three-membered rings; ring opening under acid catalysis furnishes the corresponding glycosides, whichdepending on the electrophile Xare also employed for 2-deoxyglycoside synthesis. Glycals also can be transformed into derivatives that have at C-2 an electron-withdrawing group and are amenable to Michael-type addition. A good example are 2-nitroglycals. In this case, glycoside bond formation is achieved under base catalysis and leads to 2-deoxy-2-nitroglycosides. These intermediates are readily converted into 2-amino-2-deoxyglycosides, which are constituents of almost all glycoconjugates. This 2-nitroglycal concatenation has been extensively investigated with 2-nitrogalactal derivatives. When alcohols are used as nucleophiles and strong bases used as catalysts, the result is primarily or exclusively the alpha-galacto-configured adducts. Some studies show that weaker bases may lead to preferential formation of the beta-galacto-configured products instead. The reaction was very successfully extended to other nucleophiles and also to other 2-nitroglycals that undergo base-catalyzed stereoselective Michael-type additions. Thus, 2-nitroglycals are versatile synthons in glycoconjugate and natural-products synthesis, and it is foreseeable that many more applications will be based on these readily available and highly functionalized skeletons.

N-chlorosuccinimide/sodium iodide: a convenient source of N-iodosuccinimide. Synthesis of α-iodo carbonyl compounds and trans-1,2-iodoacetates

Equimolar amounts of N-chlorosuccinimide and sodium iodide in acetone are found to be a conveinent source of N-iodosuccinimide using which trans-1,2-iodoacetates and α-iodo carbonyl compounds have been prepared from olefins and enol silyl ethers respectively.

Ceric ammonium nitrate-catalyzed azidation of 1,2-anhydro sugars: application in the synthesis of structurally diverse sugar-derived morpholine 1,2,3-triazoles and 1,4-oxazin-2-ones

Azidation of 1,2-anhydro sugars with NaN(3) in CH(3)CN by using a catalytic amount of ceric ammonium nitrate has been accomplished in a regio- and stereoselective manner. Various 1,2-anhydro sugars produced 2-hydroxy-1-azido sugars in good yields which, in turn, were converted to structurally diverse sugar-derived morpholine triazoles and sugar oxazin-2-ones. These sugar derivatives were tested against various commercially available glycosidases, and two of them were found to be active in the micromolar range.

Chlorotrimethylsilane catalysed acylation of alcohols

A variety of alcohols are converted into the corresponding acetates upon treatment with acetic anhydride and catalytic amount of chlorotrimethylsilane in acetonitrile (or dichloromethane).

Acetyl chloride-silver nitrate-acetonitrile: a reagent system for the synthesis of 2-nitroglycals and 2-nitro-1-acetamido sugars from glycals.

A new reagent system comprising acetyl chloride, silver nitrate, and acetonitrile has been developed for the synthesis of 2-nitroglycals from the corresponding glycals. Under certain conditions, the formation of 2-nitro-1-acetamido sugars has also been observed. In addition, a few other non-carbohydrate-derived olefins also gave the corrresponding conjugated nitroolefins.

Synthesis and glycosidase-inhibitory activity of novel polyhydroxylated quinolizidines derived from D-glycals

A number of structurally novel polyhydroxylated quinolizidines have been prepared starting from 2-deoxyglycosylamines which in turn were derived from D-glycals by following a methodology developed in our laboratory. In our strategy, Grignard reaction and ring-closing metathesis (RCM) reactions are the key steps to construct the desired skeletons. All synthesized final molecules were checked for glycosidase inhibition activity, and some were found to be selective for certain glycosidases.

N-halosuccinimide/AgNO3-efficient reagent systems for one-step synthesis of 2-haloglycals from glycals: application in the synthesis of 2C-branched sugars via Heck coupling reactions.

An expedient one-step synthesis of 2-iodoglycals and 2-bromoglycals from glycals using NIS/AgNO3 and NBS/AgNO3 as reagent systems has been developed. The utility of these 2-haloglycals has been demonstrated by converting them into 2C-branched glycals via the Heck coupling reaction. Ferrier reaction of tri-O-acetyl-2-iodoglycals followed by Heck coupling reaction with methyl acrylate leads to 2C-branched O-glycosides.