Relative and Absolute Configuration of the 3,12‐Dihydroxypalmitic Acids

The relative and absolute configuration of (+)‐3,12‐dihydroxypalmitic acid, a constituent of the Ipomea operculata M. resin, has been determined by synthesis. Dimethyl L ‐malate was converted via ( S )‐(+)‐ 1 into the oxirane ( S )‐(‐)‐ 2 . Reaction of (‐)‐ 2 with the Grignard reagent of 8‐benzyloxybromooctane provided ( S )‐(+)‐ 3 in 84% yield, and this was converted into the aldehyde ( S )‐(‐)‐ 6 via ( S )‐(‐)‐ 4 and ( S )‐(‐)‐ 5 . Reaction with the lithium enolate of methyl acetate gave 7 and 8 , which could be converted via 9 and 10, 11 and 12, 13 and 14 into the lactones (4 S ,13 S )‐(+)‐ 15 and (4 R ,13 S )‐(+)‐ 16 and finally into the methyl esters (3 S ,12 S )‐(+)‐ 17 and (3 R ,12 S )‐(+)‐ 18 and acids (‐)‐ 19 and (+)‐ 20 . The erythro configuration of (+)‐ 17 was established by a stereoselective synthesis starting from ( S )‐(‐)‐ 2 via ( S )‐(+)‐ 21 , (+)‐ 22 , (+)‐ 23 , the Grignard reagent of (+)‐ 24 and ( R )‐(+)‐2‐(2‐benzyloxyethyl)oxirane to give (3 S ,12 S )‐(‐)‐ 25 , (‐)‐ 26 , (+)‐ 27 and (+)‐ 28 , which could be oxidized to the diacetoxy acid (3 S ,12 S )‐(+)‐ 29 . Saponification and esterification gave (3 S ,12 S )‐(‐)‐ 19 and (3 S ,12 S )‐(+)‐ 17 , with properties identical to those of (+)‐ 17 obtained from the resin glycoside.