83(P-2) Application of Torulasapora delbrueckii-mediated reduction in natural product synthesis
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A yeast strain, Torulaspora delbrueckii IFO10921 catalyzes the enantiotopic group-selective, and enantioface-selective reduction of 2-methyl-2-(3-oxoalkyl)cycloalkane-1,3-diones to give stereochemically pure forms of bicyclic hemiacetals. These yeast-mediated reduction products are the equivalents of hydroxyketones, and the subsequent chemical transformation to bicyclic compounds warranted their stereochemistries and stereochemical purities. Next, we achieved a novel approach to the enantiomerically pure forms of 2-alkenyl-3-hydroxy-2-methylcycloalkanones such as 14. Hemiacetals 5 and 9 served as the unique precursors, which underwent β-fragmentation of the corresponding alkoxy radicals to give eventually β-acetoxyketones 15 and 16 with 2-alkenyl substituent. This transformation was realized under the reflux condition of conbined use of PhI(OAc)_2, Cu(OAc)_2 and 2,6-lutidine in benzene in 39-65% yield. Through this fragmentation reaction, part of the original hemiacetal skeleton was converted to the protecting group of the newly liberated hydroxy group as the form of acetate. To demonstrate the synthetic potential of above β-acetoxyketones 15 and 16, we have developed straightforward routes to highly functionalized cyclohexanones and cyclopentanones, towards the syntheses of natural products. Carbonyl group of 15 was protected as 1,3-dioxolane and the subsequent ozonolysis and the reductive workup yielded a 2-alkoxymethyl-3-hydroxy-2-methylcyclohexanone equivalent 18. Hydroxyl groups of 18 could be protected with TBS and benzyl groups, and the subsequent methylation to give 20 and 22, which would be useful for synthesis of diterpenoid, such as triptocallol. On the other hand, a sterically congested cyclopentenone 27, possessing three functional groups directly attached to a quaternary chiral center, was efficiently obtained from 16. The introduction of two independent side chains was successful to provide 30, a key intermediate to madindoline.
