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=(CH 2 ) 8 Me] 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 Et 3 N and Na 2 SO 4 in t-BuOMe at 45°C (E=68), and for the (S)-selective hydrolysis with H 2 O 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%).