1952 Volume 72 Issue 3 Pages 418-423
In spite of the report that Nargund and the others succeeded in total synthesis of santonin, Clemo and the others countered that the formation of its intermediate, α-(2-hydroxy-3-ketocyclohexyl)-propionic lactone (V), was not possible, and the present authors also confirmed that such could not be formed by the Paranjape method. In order to find a new synthetic procedure, the authors carried out the following reaction. The double bond of α-(cyclohexen-(2)-yl)-propionic acid (XI) was hydroxylated to allow formation of a lactone ring between the hydroxyl group in C2 and the carboxyl group in the side-chain, and the hydroxyl in the C3-position was oxidized to a carbonyl with chromic acid by which (V) was successfully obtained. Similar hydroxylation of (cyclohexen-(2)-yl)-methylmalonic acid (X) with permanganate or organic peracid results in lactonization and subsequent oxidation of the hydroxyl in 3-position and decarboxylation, or decarboxylation followed by oxidation, also gives (V). This synthetic procedure can also be applied to the esters or amides corresponding to the acids of (X) and (XI). Of the four possible isomers of (V), one kind of racemate was obtained as crystals of m.p. 87°, while the other two were obtained as oily substances. The semicarbazone described by Paranjape, et al., is different from the semicarbazones of any of the above three racemates.
