Chemoenzymatic Route to Both Enantiomers of a 1‐Isopropyl‐3a‐methyloctahydroinden‐4‐one Derivative: A Synthetic Intermediate for Sesqui‐ and Diterpenoids

Abstract

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 (reface 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.

Substituted Pyrroles via Olefin Cross-Metathesis

“…Accordingly, conversion of aldehyde 6 to allylic amine derivative 7 was readily achieved via the corresponding sulfone . Next, CM of 7 with enone 8 delivered aminoenone 9 in 50% yield. Heck reaction of this species (with bromobenzene) was demanding (cf .…”

Enzyme-Mediated Synthesis of Sesquiterpenes

“…Also a large number of asymmetric 1,3-diketones have been successful chosen as substrates in microbial biotransformations, but only few of these processes have been used for the synthesis of terpenic compounds. Some noteworthy exceptions concern the yeast-mediated reduction of diketo derivatives 50 [46], 53 [47] and 56 [48]. Baker's yeast converted the spiro-derivative 50 into enantiopure keto-alcohol 51, which is a suitable starting material for the preparation of terpenes having a pentalene framework 52.…”

Update 1 of: Enantioselective Enzymatic Desymmetrizations in Organic Synthesis

“…Sugai and co-workers have investigated the substrate specificity of the reduction of different triketones with the yeast strain Torulaspora delbrueckii IFO10921 . They have carried out the enantioselective reduction of the prochiral triketones 252a − d shown in Scheme .…”