Chemoenzymatic Synthesis of (+)-α-Polypodatetraene and Methyl (5R,10R,13R)-Labda-8-en-15-oate

• Published in: Chemical & Pharmaceutical Bulletin Vol. 56; no. 1; pp. 118 - 123
• Main Authors: Masako KINOSHITAa, Takahiro MIYAKEa, b, Yuusuke ARIMAa, Minako OGUMAa, Hiroyuki AKITAa
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 2008
• ISSN: 0009-2363; 1347-5223

The reported enzymatic resolution products {acetate of (1S,4aS,8aS)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal} (8aS)-5 (＞99% ee)] and [(1R,4aR,8aR)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal (8aR)-4 (98% ee) were converted to (＋)-α-polypodatetraene (1) and methyl (5R,10R,13R)-labda-8-en-15-oate (2), respectively. For the synthesis of (5R,10R,13R)-2, chiral isoprene congener (3S)-26 corresponding to the right part of 2 was synthesized based on the lipase-assisted resolution of (±)-2-methyl-3 (p-methoxyphenyl)propanol (17). The chiral structural unit A possessing decaline ring system attached with three methyl group is the important nuclei found in a variety of natural products such as drimane sesquiterpenes and other terpenes. Among them, (＋)-α-polypodatetraene (1)1) and methyl (5R,10R,13R)-labda-8-en-15-oate (2)2) are typical compounds (Chart 1). For the synthesis of these compounds, (8aS)- and (8aR)-β-keto esters (3) are the desirable compound as starting material.