Continuous-flow enzymatic resolution strategy for the acylation of amino alcohols with a remote stereogenic centre

Synthesis of calycotomine enantiomers

László Schönstein, E. Forró, F. Fülöp

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21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)202-206
Number of pages5
JournalTetrahedron Asymmetry
Volume24
Issue number4
DOIs
Publication statusPublished - Feb 28 2013

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Amino alcohols
Amino Alcohols
acylation
Acylation
Enantiomers
enantiomers
alcohols
Tetrahydroisoquinolines
Enantioselectivity
synthesis
Methanol
esters
Esters
methyl alcohol
heliamine

ASJC Scopus subject areas

  • Organic Chemistry
  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Catalysis

Cite this

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title = "Continuous-flow enzymatic resolution strategy for the acylation of amino alcohols with a remote stereogenic centre: Synthesis of calycotomine enantiomers",
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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T1 - Continuous-flow enzymatic resolution strategy for the acylation of amino alcohols with a remote stereogenic centre

T2 - Synthesis of calycotomine enantiomers

AU - Schönstein, László

AU - Forró, E.

AU - Fülöp, F.

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N2 - 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.

AB - 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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