The reaction of 2-hyroxyaldehyde derivatives 6,7,9,12,14 and 15 having R -configuration and dihydroxyacetone phosphate (DHAP) 5 gave stereoselective aldol equivalents of cyclic compound 19 and 21 via linear aldols or linear aldols 22,23 and 24 in the presence of FDP aldolase followed by acid phosphatase treatment. Contrary, the reaction of 2-hydroxyaldehyde derivatives having S-configuration 16 and 17 and 5 gave an epimeric mixture of aldols 25 and 26 via epimerization of the aldehydes in the same conditions. This fact expects that a diastereo-facial selective reaction to the aldehydes having R-configuration took place. Reductive removal of the primary hydroxy group from 27a, 27b derived from 19, and 30 derived from 23 by Barton reaction (radical reaction) and by LiAlH_4 reduction (S_N2 reaction), respectively, gave dehydrated compounds. These compounds gave pentamycin C-11-C-16 and C-9-C-16 fragments 29 and 31 with right stereochemistry. Based on the above expectation of diastereo-facial selective reactions, we tried aldehydes with sulfer or chlorine at 2-position 34a-34j. Although the former 34a-34h gave nothing of the aldols, the latter 34i and 34j gave the corresponding aldols 35i (24% yield) and 35j (27% yield) with diastero-facial selection. This means that we can obtain optically active non-carbohydrate key intermediates by controlling three carbon units with chlorine by differentiating from hydroxy groups starting from optically inactive RS-aldehydes and 5 in the presence of aldolase. Now, we are intending to determine the configuration of the chlorine of 35i and 35j. We explore a new method by controlling stereochemistry with an enzyme and followed by appropriate chemical transformations to non-carbohydrate key intermediates by carbon-carbon bond formation.
