Development of Novel Chiral Building Blocks and Their Utilization in the Synthesis of Physiologically Active Compounds

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The object of this study was to develop highly functionalized chiral building blocks and their utilization in the synthesis of physiologically active substances, where we have decided to exploit a monoterpene, carvone, as a starting material, since monoterpenes have long being recognized as useful chiral precursors in the synthesis of quite different structural classes of natural products. Thus (+)-and(-)- carvone were converted into the corresponding cyclopentanone derivatives by three-steps involving the Favorskii type rearrangement, in good yields, respectively. This chiral cyclopentanone has different three types of functional groups, hence the chemical modification of all the carbon atoms on the cyclopentanone could easily beachieved.Based on the above concept, the synthesis of thienamycin, a carbapenem antibiotic, was established starting from the chiral cyclopentanone. The synthetic strategy developed here was also applied to the synthesis of its 1beta-methyl derivative and other carbapenem antibiotics. Furthermore, thy syntheses of (+)-eldanolide, (-)-cis- whisky lactone, (-)-neonepetalactone, and oudemansin A were also achieved, in which a regioselective bond cleavage reaction, newly developed by us, of the cyclopentanone played an important role.These results clearly indicated that the cyclopentanone, readily accessible from a monoterpene, carvone, is a useful chiral synthon in the synthesis of various types of physiologically active compounds.