Stephen P. Douglas

Silver Trifluoromethanesulfonate(Triflate) Activation of Trichloroacetimidates in Glycosylation Reactions

Abstract Chemical syntheses of biologically active oligosaccharides, glycolipids and glycopeptides requires efficient stereospecific glycosylation reactions.2 One of the most effective glycosylation methods involves activation of anomeric imidates, particularly mchloroacetimidates, by Lewis acids such as boron trifluoride etherate (BF3·OEt2), mmethylsilyl mfluoromethanesulfonate (TMSOTF)3 and mfluoromethanesulfonic anhydride.4 In a recent example from this laboratory, BF3·OEt2, has been used to promote the glycosylation of methyl 2,3,6-tri-O-benzoyl-B-D-galactopyranoside (I)5 with 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-B-D-galactopyranosyl mchloroacetimidate (I): see Scheme 1. The expected β1-4-linked disaccharide III was obtained in 40% yield. The yield was so low since both the α-anomer and a 1-3-linked disaccharide were formed as by products, the latter in particularly large quantities (cf. Ref.7). The 1-3 disaccharide could be formed from a product of acid-catalyzed 3,4-migration of the benzoyl grou...

Polymer-supported syntheses of oligosaccharides: Using dibutylboron triflate to promote glycosylations with glycosyl trichloroacetimidates

Abstract Dibutylboron triflate as a promoter of glycosylations with glycosyl trichloroacetimidates compares favourably with most other promoters.

Metathesis of oligosaccharides. Relative stabilities of activated and deactivated glycosides of polyethylene glycol.

Abstract The preparation of glycosides and orthoesters of the monomethylether of polyethyleneglycol are described. The attempted glycosylation of these glycosides unexpectedly led to glycosyl exchange instead of the expected oligosaccharides. This observation suggests that PEG as aglycon acts both as a leaving group and a nucleophile. A hypothesis explaining metathesis of oligosaccharides under glycosylation conditions has been formulated.

Bridged ring a steroids: total synthesis of (±)-14β-hydroxy-1β,4β-methano-5β,8α,9β-androstane-7,17-dione

A modification of the Torgov steroid synthesis in which a vinyl methyl ether group in ring B stabilizes the critical cationic intermediate has been used to synthesize the title compound (15), whose structure has been confirmed by X-ray crystallographic analysis.

[10] Galactosylation of nucleosides at 5′-position of pentofuranoses

Publisher Summary The evaluation of biological activity requires absolutely pure compounds in relatively large quantities. Because glycosylation of carbohydrate primary hydroxyls usually proceeds smoothly, in principle such galactosylated nucleosides should be obtainable by organic synthesis. Several synthetic analogs of naturally occurring nucleosides are clinically useful anticancer or antiviral agents. A practical problem with their use arises from the low selectivity of such agents: they kill normal cells, albeit more slowly, as well as neoplastic or virally infected cells. An increase in selectivity would substantially increase the curative potential of such drugs. For instance, if the cytotoxicity can be abolished by glycosylation of the drug, and if a suitable glycosidase were present only in a cancer cell, then this glycosylation would provide the needed increase in the selectivity.