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Chemoenzymatic Route to Both Enantiomers of a 1‐Isopropyl‐3a‐methyloctahydroinden‐4‐one Derivative: A Synthetic Intermediate for Sesqui‐ and Diterpenoids
Author(s) -
Fujieda Shigeo,
Tomita Mina,
Fuhshuku Kenichi,
Ohba Shigeru,
Nishiyama Shigeru,
Sugai Takeshi
Publication year - 2005
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200505034
Subject(s) - chemistry , diastereomer , stereochemistry , hemiacetal , intramolecular force , ketone , stereoselectivity , chiral auxiliary , enantiomer , enantioselective synthesis , desymmetrization , organic chemistry , catalysis
On the way to a chemoenzymatic synthesis of a key intermediate for sesquiterpenoids and diterpenoids, 2‐methyl‐2‐(4‐methyl‐3‐oxopentyl)‐1,3‐cyclohexanedione was reduced with the whole cells of yeast biocatalysts. Torulaspora delbrueckii NBRC10921 reduced a cyclic ketone of three carbonyl groups in an enantiofacially selective manner ( re ‐face attack), but there was poor enantiotopic group selectivity between two carbonyl groups on the cyclohexane ring to yield a mixture of diastereomeric products. Candida floricola IAM13115 reduced mainly the pro ‐( R ) carbonyl group. In contrast, the reduction proceeded in an enantiofacially poorly selective manner to give another set of diastereomeric products. In both cases, another carbonyl group on the side chain worked as a ‘trapping arm’ of the resulting secondary alcohol. The diastereomeric products were effectively separated as the ‘ syn ’ or ‘ cis ’ isomer exclusively exist in the intramolecular hemiacetal structure, while ‘ anti ’ or ‘ trans ’ isomer being an equilibrated mixture of cyclic hemiacetal and open‐chain hydroxyketone ( ca. 0.7 : 1). Starting separately from the enantiomerically enriched products as above, both enantiomers of the target compound, a key intermediate for terpenoids, were efficiently prepared via stereoselective ring closure under pinacol coupling reaction conditions. Furthermore, a daucane sesquiterpene intermediate, a hydroazulene derivative, was provided after one‐carbon homologation of the six‐membered ring.