Chemoenzymatic preparation of enantiopure homoadamantyl β-amino acid and β-lactam derivatives

Zsuzsanna Cs Gyarmati, Arto Liljeblad, G. Argay, A. Kálmán, G. Bernáth, Liisa T. Kanerva

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Racemic cis-10-azatetracyclo[7.2.0.12,6.14,8]- tridecan-11-one was prepared from homoadamant-4-ene by chlorosulfonyl isocyanate addition. The trans-formation of the β-lactam to the corresponding β-amino ester followed by Candida antarctica lipase A-catalyzed enantioselective (E > > 200) N-acylation with 2,2,2-trifluoroethyl butanoate afforded methyl (1R,4R,5S,85)-5-aminotricyclo[4.3.1.1 3,8]undecane-4-carboxylate and the (1S,4S,5R,8R)-butanamide with > 99% ee at 50% conversion. Alternatively, transformation of the β-lactam to the corresponding N-hydroxymethyl-β-lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase-catalyzed enantioseletive O-acylation provided the (1S,4S,6R,9R)-alcohol (ee = 87%) and the corresponding (1R,4R,6S,9S)-butanoate (ee > 99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)-butanoate, 2,2,2-trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)-alcohol with time.

Original languageEnglish
Pages (from-to)566-572
Number of pages7
JournalAdvanced Synthesis and Catalysis
Volume346
Issue number5
DOIs
Publication statusPublished - May 2004

Fingerprint

Lactams
Amino acids
Acylation
Lipases
Derivatives
Lipase
Amino Acids
Alcohols
Butyric acid
Butyric Acid
Candida
Hydrolysis
Esters
Enzymes

Keywords

  • β-amino acid
  • β-lactam
  • Enantioselective acylation
  • Homoadamantyl derivative
  • Lipase catalysis

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Organic Chemistry
  • Catalysis

Cite this

Chemoenzymatic preparation of enantiopure homoadamantyl β-amino acid and β-lactam derivatives. / Gyarmati, Zsuzsanna Cs; Liljeblad, Arto; Argay, G.; Kálmán, A.; Bernáth, G.; Kanerva, Liisa T.

In: Advanced Synthesis and Catalysis, Vol. 346, No. 5, 05.2004, p. 566-572.

Research output: Contribution to journalArticle

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AU - Gyarmati, Zsuzsanna Cs

AU - Liljeblad, Arto

AU - Argay, G.

AU - Kálmán, A.

AU - Bernáth, G.

AU - Kanerva, Liisa T.

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N2 - Racemic cis-10-azatetracyclo[7.2.0.12,6.14,8]- tridecan-11-one was prepared from homoadamant-4-ene by chlorosulfonyl isocyanate addition. The trans-formation of the β-lactam to the corresponding β-amino ester followed by Candida antarctica lipase A-catalyzed enantioselective (E > > 200) N-acylation with 2,2,2-trifluoroethyl butanoate afforded methyl (1R,4R,5S,85)-5-aminotricyclo[4.3.1.1 3,8]undecane-4-carboxylate and the (1S,4S,5R,8R)-butanamide with > 99% ee at 50% conversion. Alternatively, transformation of the β-lactam to the corresponding N-hydroxymethyl-β-lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase-catalyzed enantioseletive O-acylation provided the (1S,4S,6R,9R)-alcohol (ee = 87%) and the corresponding (1R,4R,6S,9S)-butanoate (ee > 99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)-butanoate, 2,2,2-trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)-alcohol with time.

AB - Racemic cis-10-azatetracyclo[7.2.0.12,6.14,8]- tridecan-11-one was prepared from homoadamant-4-ene by chlorosulfonyl isocyanate addition. The trans-formation of the β-lactam to the corresponding β-amino ester followed by Candida antarctica lipase A-catalyzed enantioselective (E > > 200) N-acylation with 2,2,2-trifluoroethyl butanoate afforded methyl (1R,4R,5S,85)-5-aminotricyclo[4.3.1.1 3,8]undecane-4-carboxylate and the (1S,4S,5R,8R)-butanamide with > 99% ee at 50% conversion. Alternatively, transformation of the β-lactam to the corresponding N-hydroxymethyl-β-lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase-catalyzed enantioseletive O-acylation provided the (1S,4S,6R,9R)-alcohol (ee = 87%) and the corresponding (1R,4R,6S,9S)-butanoate (ee > 99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)-butanoate, 2,2,2-trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)-alcohol with time.

KW - β-amino acid

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KW - Enantioselective acylation

KW - Homoadamantyl derivative

KW - Lipase catalysis

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