Synthesis of β -Cyperone via Fungal Hydroxylation of thujone-derived tricyclic cyclopropanes

✍ Scribed by James P. Kutney; Jürgen Wagner; Gary M. Hewitt

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: German
• Weight: 906 KB
• Volume: 77
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19940770704

✦ Synopsis

Synthesis of optically active sesquiterpenes with a eudesmane C-skeleton from the chiral starting material thujone involves transformation of a tricyclic intermediate (I R,2R,4S)-I ,7-dimethyl-4-(l-methylethyl)tricyclo[4.4.0.02~4]dec-6-en-8-one (2) into the bicyclic compoundp -cyperone (5). Hydroxylation of 2 at C(5) or C(11) permits subsequent opening of the cyclopropane ring and rearrangement top -cyperone. In this publication, studies involving hydroxylation of 2 by fungal cultures are presented. The resultant products are useful intermediates in efficient synthesis of eudesmane sesquiterpenes. Of five fungi tested, Rhizopus oryzae ATCC 11 145 proved most versatile. It hydroxylates at the exoyclic C(11) position in high yield (70%) and, to a lesser extent, at C(5) (5%).

Enzymatic activity appears at the end of growth phase and at least 2.2 g of 2 per liter can be metabolized without significant loss of product yield. A second fungus, Cunninghamella echinulata ATCC 9244, proved most useful for hydroxylation of derivatives of 2 for the preparation of derivatives ofp -cyperone, although product yields were low (2-20%), some derivatives were nonreactive, and hydroxylation at C(9) occurred. The relationship between precursor structure and enzyme affinity is discussed.