Continuous-flow enzymatic resolution strategy for the acylation of amino alcohols with a remote stereogenic centre: synthesis of calycotomine enantiomers |
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Authors: | László Schönstein Enikő Forró Ferenc Fülöp |
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Affiliation: | Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6701 Szeged, Hungary |
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Abstract: | Both enantiomers of calycotomine (R)-5 and (S)-5 were prepared through the CAL-B-catalysed asymmetric O-acylation of N-Boc-protected (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)methanol [(±)-3)]. The optimum conditions for the enzymatic resolution were determined under continuous-flow conditions, while the preparative-scale resolution of (±)-3 was performed as a batch reaction with high enantioselectivity (E >200). The resulting amino alcohol (S)-3 and amino ester (R)-4, obtained with high enantiomeric excess (ee = 99%), were transformed into the desired calycotomine (S)-5 and (R)-5 (ee = 99%). A systematic study was carried out in a continuous-flow system on the O-acylation of tetrahydroisoquinoline amino alcohol homologues (±)-1 to (±)-3 containing a remote stereogenic centre. |
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