GLYCOSYL ALPHA-AMINO-ACIDS VIA STEREOCONTROLLED BUILDUP OF A PENALDIC ACID EQUIVALENT - A NOVEL SYNTHETIC APPROACH TO THE NUCLEOSIDIC COMPONENT OF THE POLYOXINS AND RELATED SUBSTANCES

A novel approach to glycosyl a-amino acids is exemplified by the stereocontrolled and asymmetric synthesis of thymine polyoxin C (4) from the known (serine-derived) penaldic acid equivalent 5. The overall synthetic strategy involves four distinct phases: (1) diastereoselective addition of a 3-carbon nucleophile (lithio ethyl propiolate) to the protected serinal derivative (5 → 54), (2) stereocontrolled elaboration of the 5-amino-5-deoxyallofuranose moiety via cis-hydroxylation of a 4-substituted butenolide (54 → 63), (3) release of the latent a-amino acid moiety in a suitably protected form (63 → 69), and (4) stereo-and regioselective nucleoside formation using Vorbruggen's glycosylation methodology followed by deprotection (69 → 4). A similar route employing lithiopropiolaldehyde dimethyl acetal as the 3-carbon nucleophile led to the formation of stereoisomeric 5-amino-5-deoxymannofuranuronic acid nucleosides (cf. 42 and 46) along with the novel acyclic 1-methoxy-D-allo-hexouronate nucleosides 52/53. © 1990, American Chemical Society. All rights reserved.