Both enantiomers of the antitumour-active alkaloid crispine A (ee = 95%) were synthesised through the Burkholderia cepacia lipase-catalysed acylation of the primary hydroxy group of N-Boc-protected 1-(3- hydroxypropyl)-6,7- bis(methyloxy)-1,2,3,4-tetrahydroisoquinoline (±)-3 and the enantioselective hydrolysis of the corresponding O-decanoate (±)-4 [R = (CH2)8Me] with a remote, four-atom distant stereogenic centre. High enantioselectivities were observed for the (S)-selective O-acylation with vinyl decanoate in the presence of Et3N and Na 2SO4 in t-BuOMe at 45 °C (E = 68), and for the (S)-selective hydrolysis with H2O in t-BuOMe at 45 °C (E = 52). The enzymatic resolutions, performed in two steps, afforded the key alcohol and ester enantiomers with high enantiomeric excesses (ee≥94%). Ring-closure reactions of alcohol enantiomers (+)-3 and (-)-3 with thionyl chloride afforded the desired crispine A enantiomers (+)-1 and (-)-1 (ee≥95%).
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry