Syntheses of Natural Products and Biologically Active Compounds by Means of Enantioselective Deprotonation Strategy.

Abstract

Enantioselective deprotonation reactions of prochiral 4, 4-disubstituted cyclohexanone, 3-substituted cyclobutanones and 3, 5-dioxygenated cyclohexanones with a chiral lithium amide bases in the presence of silylating agents, were carried out to give the corresponding silyl enol ethers. The silyl enol ether obtained from 4-methyl-4-tolylcyclohexanone was converted to (+) -α-cuparenone. On the other hand, the silyl enol ethers derived from 3-substituted cyclobutanones were utilized in the synthesis of naturally occurring (-) -methylenolactocine and several kinds of lignan lactones, and also in the synthesis of medicinally important compound, (R) - (-) -rolipram. Moreover, the silyl enol ethers prepared from prochiral 3, 5-dioxygenated cyclohexanones were employed as the starting materials in the synthesis of biologically important compounds, such as HMG-CoA reductase inhibitor and antiobesity agent, tetrahydrolipstatin, with the opposite mode of asymmetric induction even by using the same chiral amide base. Finally, a synthetic procedure for enantiomerically enriched 5-hydroxycyclohex-2-enone was established by elimination of the alkoxide group in the chiral silyl enol ether, which was further transformed into an inositol phosphatase inhibitor.