A Ring Contraction of 2,3-Di-O-Silylated Thiopyranosides To Give Thiofuranosides under Mildly Acidic Conditions

Abstract

A pyranose ring contraction of ethyl 1-thio-β-d-galactopyranosides has been discovered that proceeds with retention of aglycon under mildly acidic conditions (aq TFA in CH2Cl2). Key factors for success of this rearrangement are the presence of bulky silyl (TIPS or TBDPS) substituents at both O-2 and O-3 and a free hydroxy group at C-4 (derivatives with acid-labile protective groups at O-4 will also engage in this reaction). The rearrangement cleanly proceeds for 2,3-di-O-TIPS derivatives with two hydroxy groups at C-4 and C-6, acid-labile TES groups at O-4 and O-6, or one acyl substituent (Bz, ClAc) at O-6. A possibility to switch the direction of the debenzylidenation reaction in 4,6-O-benzylidene-2,3-di-O-TIPS/TBDPS derivatives by the choice of an acid (TFA, which cleanly gives furanose, versus AcOH, which cleaves benzylidene acetal only) may present an advantage in the divergent synthesis of selectively protected glycosyl donors (either in furanose or pyranose form) useful for the synthesis of biologically important oligosaccharides.

Catalyst-free regioselective acetylation of primary hydroxy groups in partially protected and unprotected thioglycosides with acetic acid

“…1,75 We have recently reported that the cleavage of 4,6-O-benzylidene group in derivatives of b-congured ethyl 1-thio-b-D-galactopyranoside with silyl (TIPS or TBDPS) groups at O-2 and O-3 with 80% aq AcOH (80 C, 1 h) gave the expected 4,6-diols in 68-75% yields, while treatment with aq TFA in CH 2 Cl 2 led to pyranose ring contraction. 76 To study the effect of anomeric conguration on the result of treatment of benzylidene acetals with acids, we synthesised ethyl 4,6-O-benzylidene-1-thio-a-Dgalactopyranoside (1) and the corresponding 2,3-O-TIPS 2 3 with TBDPS groups at O-2 and O-3 under identical conditions (according to method B) ( Fig. 1) at the same concentration (c ¼ 48 mmol L À1 ) gave diol 8 and 6-O-acetylated product 9 in 39 and 35% yields, respectively (Fig.…”

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

“…Changes in the conformations of monosaccharides expectedly accompany their modification with different functional groups. Thus, spatial repulsion of silyl groups results in inversion or distortion of the pyranoside ring [1–2], which strongly modifies the chemical behaviour of the pyranoside substrate by influencing the spatial environment of the reaction center and changing stereoelectronic effects [3–5]. A rather complex case is observed for sulfate groups; in addition to van der Waals interactions their negative charges contribute to the electrostatic forces.…”

Synthesis of vicinal dideoxy-difluorinated galactoses

“…The synthesis of the corresponding protected furanose isomer 17b was investigated starting from the pyranose derivatives. Many excellent pyranose-to-furanose isomerisation protocols have been reported, [45][46][47][48][49][50] which unfortunately are not all applicable starting from 16a due to the presence of the vicinal fluorine motif at C2 and C3. We first envisaged to obtain the furanose 17b following an acetylation/isomerisation precedent with 2-deoxy-2fluorogalactose 21 from Liu and co-workers (Scheme 3).…”