title: Biochemical approaches to the synthesis of ethyl 5-(s)-hydroxyhexanoate and 5-(s)-hydroxyhexanenitrile.
abstract: Three different biochemical approaches were used for the synthesis of ethyl 5-(S)-hydroxyhexanoate 1 and 5-(S)-hydroxyhexanenitrile 2. In the first approach, ethyl 5-oxo-hexanoate 3 and 5-oxo-hexanenitrile 4 were reduced by Pichia methanolica (SC 16116) to the corresponding (S)-alcohols, ethyl (S)-5-hydroxyhexanoate 1 and 5-(S)-hydroxyhexanenitrile 2, with an 80-90% yield and >95% enantiomeric excess (e.e). In the second approach, racemic 5-hydroxyhexanenitrile 5 was resolved by enzymatic succinylation, leading to the formation of (R)-5-hydroxyhexanenitrile hemisuccinate and leaving the desired alcohol 5-(S)-hydroxyhexanenitrile 2 with a yield of 34% (50% maximum yield) and >99% e.e. In the third approach, enzymatic hydrolysis of racemic 5-acetoxy hexanenitrile 6 resulted in the hydrolysis of the R-isomer to provide 5-(R)-hydroxyhexanenitrile, leaving 5-(S)-acetoxyhexanenitrile 7 with a 42% yield (50% maximum yield) and >99% e.e.
authors.affiliation: Enzyme Technology, Process Research & Development, Pharmaceutical Research Institute, Bristol-Myers Squibb, P.O. Box 191, NJ 08903, New Brunswick, USA
authors.forename: V B.
authors.initials: VB
authors.lastname: Nanduri
authors.forename: R L.
authors.initials: RL
authors.lastname: Hanson
authors.forename: A
authors.initials: A
authors.lastname: Goswami
authors.forename: J M.
authors.initials: JM
authors.lastname: Wasylyk
authors.forename: T L.
authors.initials: TL
authors.lastname: LaPorte
authors.forename: K
authors.initials: K
authors.lastname: Katipally
authors.forename: H -J.
authors.initials: H
authors.lastname: Chung
authors.forename: R N.
authors.initials: RN
authors.lastname: Patel