THE USE OF MICROBIAL AND ENZYMATIC FUNCTION IN ORGANIC-SYNTHESIS - TOTAL SYNTHESIS OF THE AGLYCONE OF VENTURICIDIN-A AND VENTURICIDIN-B

The synthesis of chiral synthons by means of microbial and enzymatic function and its application to the synthesis of complex, bioactive substances, the aglycone of venturicidins A and B are reviewed. 1) The synthesis of chiral synthons having two chiral centers are described based on the microbial asymmetric reduction of alpha-methyl beta-keto esters or enzymatic asymmetric hydrolysis of alpha-methyl beta-acetoxy esters. 2) The new chiral synthons synthesized in 1) have been successfully applied for the total syntheses of oudemansins A and B. 3) Purification and properties of the asymmetric reduction enzyme of alpha-methyl beta-keto esters in Saccharomyces cerevisiae or Saccharomyces fermentati were investigated. 4) Formal total synthesis of (-)-indolmycin is described based on the asymmetric hydrolysis of alpha-acetoxy ester with lipases. 5) Enzymatic hydrolysis in organic solvents for kinetic resolution of water-insoluble alpha-acyloxy esters with immobilized lipases is described. 6) The first total synthesis of the aglycone of venturicidins A and B has been successfully achieved from the new chiral synthon based on the developed method in 1).