Reaction of O-Benzyl- and 4,6-O-Benzylidene-d-Gluco- and d-Galactopyranose Derivatives with Amide-Stabilized Sulfur Ylides:  Stereoselectivity and Reactivity

Abstract

The reaction of N,N-diethyl-2-(dimethylsulfuranylidene)acetamide (1) with protected monosaccharides has been extended to several O-benzyl- and 4,6-O-Benzylidene-d-gluco- and -d-galactopyranose derivatives. When the monosaccharide is 2,3,4,6-tetra-O-benzyl-d-glucose (6) or d-galactose (9), elimination of the 3-benzyloxy substituent occurs, to give the unsaturated epoxyamides 7 and 10, respectively, in reasonable yields and poor stereoselectivity. On the other hand, the reaction of 1 with the 4,6-O-benzylidene-d-glucopyranose derivatives 11, 14, and 17 yielded the corresponding epoxyamides 12, 15a:15b, and 18a:18b in good yields and variable stereoselectivity. In accordance with previous studies concerning the configurational assignments for the epoxide derivatives 3, 5a, and 21, obtained from 2, 4, and 20, respectively, the present article confirms the role of the hydroxyl group at C-2 on the stereselectivity of the reaction. Thus, when the C-2 OH is unprotected (4, 11, 20), the major epoxide formed has the configuration 2S, 3R (epoxyamides 5a, 12, and 21). Conversely, derivatives with the hydroxyl group protected at C-2, or 2-deoxy sugars (2, 14, and 17), yield as the major epoxides the corresponding 2R, 3S isomers (3, 15b, and 18b).

Synthesis of Di- to Hexasaccharide 1,2-Linked β-Mannopyranan Oligomers, a Terminal S-Linked Tetrasaccharide Congener and the Corresponding BSA Glycoconjugates

“…Synthesis of the Thioglycoside Mimetic. The synthesis of the glucosyl donor (23) began by treating a DMF solution of 3-O-benzylglucose, available from a one-pot procedure, 22 with benzaldehyde dimethyl acetal and a catalytic amount of acid. This solution was slowly concentrated under vacuum to remove methanol and give the benzylidene acetal derivative 20 in 94% yield.…”

“…The synthesis of compound 20 was recently reported using benzaldehyde and zinc chloride in 54% yield. 23 The diol 20 was acetylated to give 21, and the anomeric acetate could be selectively removed with benzylamine in THF to give hemiacetal 22. 24 Generation of the trichloracetimidate under standard conditions gave the glycosyl donor 23 (Figure 3).…”

“…More vigorous conditions, including the use of acetonitrile as a solvent, resulted in considerable accumulation of the other possible benzylidene acetals. The synthesis of compound 20 was recently reported using benzaldehyde and zinc chloride in 54% yield . The diol 20 was acetylated to give 21 , and the anomeric acetate could be selectively removed with benzylamine in THF to give hemiacetal 22 .…”

Aminals as Substrates for Sulfur Ylides: A Synthesis of Functionalized Aziridines and N-Heterocycles

“…Lactols and related hemiaminals, readily available synthetic intermediates, are masked electrophiles but nevertheless react readily with a range of nucleophiles including phosphorus ylides and stabilized and semistabilized sulfur ylides. These reactions occur via the ring-opened aldehyde, which is only present in very low concentrations.…”