Short Regioselective Chemoenzymatic Synthesis and Biological Evaluation of 1‐ O ‐Acyl‐2‐ O ‐(β‐ D ‐sulfoquinovopyranosyl)‐ sn ‐glycerols

A convenient chemoenzymatic synthesis of a new class of non‐natural sulfo‐glycolipids – 2‐ O ‐(β‐ D ‐sulfoquinovosyl)‐monoacylglycerols (2‐ O ‐β‐ D ‐SQMG) – derived from 2‐ O ‐(β‐ D ‐glucopyranosyl)glycerol and carrying acyl chains ofvarious lengths at the 1‐position of the sn ‐glycerol moiety, was performed with the aid of a key step involving regioselective lipase‐catalyzed acylation of 2‐ O ‐(6‐deoxy‐6‐tosyl‐β‐ D ‐glucopyranosyl)‐ sn ‐glycerol ( 4 ) at its 1‐position, reported here for the first time. Elaboration of the sugar moiety through thioacetate substitution of the selectively inserted tosyl group with subsequent Oxone ® oxidation in the presence of unprotected primary and secondary hydroxy groups efficiently afforded the target compounds, the hexanoyl, dodecanoyl, and octadecanoyl derivatives 1a – c , which were active when tested in the EBV‐EA in vitro assay for antitumor promoters. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)