A PRACTICAL SYNTHESIS OF THE DIHYDROXYETHYLENE DIPEPTIDE ISOSTERE, (2S,3R,4S) 2-[(TERT-BUTYLOXYCARBONYL)AMINO]-1-CYCLOHEXYL-3,4-DIHYDROXY-6-METHYLHEPTANE, FROM D-ISOASCORBIC ACID

The N-Boc dihydroxyethylene dipeptide isostere 7 and its N-Boc 3-(thiazol-4-yl)alanyl derivative 8 were synthesized, without purification of intermediates, from (4S,5R)-2,2-dimethyl-4-(2-methylpropyl)-5-hydroxymethyl-1,3-dioxolane (3b), in 24 and 32% overall yield, respectively. Alcohol 3b was readily prepared from inexpensive and commerically available D-isoascorbic acid in four steps. The synthesis featured a stereoselective addition of cyclohexylmethyllithium to the dimethyl hydrazone of (4S,5S)-2,2-dimethyl-4-(2-methylpropyl)-5-formyl-1,3-dioxolane (4).