抄録
A yeast strain, Torulaspora delbrueckii NBRC10921 catalyzes the regio- and enantio-selective reduction of triketone 1 to give stereochemically pure form of bicyclic hemiacetal (+)-2 in excellent enantiomeric excess. Hemiacetal (+)-2 was converted to β-acetoxyketone (+)-3 via radical fragmentation using hypervalent iodine reagent. The resulting β-acetoxy-cc,a-disubstituted cyclopentanone would be useful for syntheses of various bioactive compounds because of its multifunctionalized structure. Madindorines A and B were isolated from the culture of Streptomyces nitrosporeus K93-0711 by Omura group in 1996 as a selective inhibitor of IL-6 activity. Madindolines were expected as a treatment of osteoporosis and the chronic rheumatism, and have quaternary chiral centers and a sterically congested cyclopentendiones. Acetyl group of 3 was removed under acidic condition and the subsequent tosylation followed by inversion of the hydroxyl group with KNO_2 gave hydroxyketone 14 (d.r.=25:1). Hydroxyketone 14 was protected as TBS ether and subsequent Saegusa oxidation produced enone 11. The introduction of the two alkyl groups was successful to provide enone 17. The final stage of the synthesis was the selective cleavage of the double bond in side chain. Ozonolysis of alkene 17 in Me0H followed by treatment with Ac_20-Et_3N in CH2C12 afforded the desired methyl ester 10, the key intermediate to (+)-madindoline A.
