Total synthesis of crispine A enantiomers through a Burkholderia cepacia lipase-catalysed kinetic resolution

E. Forró, László Schönstein, F. Fülöp

Research output: Contribution to journalArticle

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Abstract

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%).

Original languageEnglish
Pages (from-to)1255-1260
Number of pages6
JournalTetrahedron Asymmetry
Volume22
Issue number11
DOIs
Publication statusPublished - Jun 2011

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Enzyme kinetics
Enantiomers
enantiomers
Lipases
Lipase
acylation
Acylation
Kinetics
kinetics
synthesis
hydrolysis
Hydrolysis
alcohols
Alcohols
Decanoates
Alkaloids
alkaloids
Enantioselectivity
closures
esters

ASJC Scopus subject areas

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

Cite this

Total synthesis of crispine A enantiomers through a Burkholderia cepacia lipase-catalysed kinetic resolution. / Forró, E.; Schönstein, László; Fülöp, F.

In: Tetrahedron Asymmetry, Vol. 22, No. 11, 06.2011, p. 1255-1260.

Research output: Contribution to journalArticle

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