SYNTHESIS OF CARBOCYCLIC ANALOGS OF 2-DEOXY-KDO

3(R),4(S)-Dihydroxy-5(R)-(1'(S),2'-dihydroxyethyl)-(S)-cyclohexanecarboxylic acid (1) and 3(R),4(S)-dihydroxy*5(R)-(l'(S),2'-dihydroxyethyl)-(R)-cyclohexanecarboxylic acid (2) have been synthesized as potential inhibitors of the enzyme CMP-Kdo synthetase. The key steps in the synthesis of 1 and 2 were a three-carbon chain extension at C-4 of the protected D-manno derivatives l-O-(tert-butyldimethylsilyl)-2,3:5,6-di-0-isopropylidene-4-0-(phenoxythiocarbonyl)-D-mannitol (5) and l,6-anhydro-2,3-O-isopropylidene-4-O-(phenoxythiocarbonyl)-β-D-mannopyranose (11a) with allyltributylstannane under radical coupling conditions and the intramolecular alkylation of l,4-dideoxy-4-C-[2'-(iert-butoxycarbonyl)ethyl]-l-iodo-2,3:5,6-di-O-isopropylidene-D-mannitol (15) to form the protected products 1 and 2. Two different routes leading to 1 and 2, both starting from D-mannose, were used. The two routes converge at 4-C-allyl-4-deoxy-2,3:5,6-di-O-isol propylidene-D-mannitol (7a), obtained as a diastereomeric mixture in one route and as a pure isomer in the other. © 1990, American Chemical Society. All rights reserved.