Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers

Efficient enzymatic resolutions are reported for the preparation of new eight-membered ring-fused enantiomeric β-amino acids [(1R,2S)-9 and (1S,2R)-9] and β-lactams [(1S,8R)-3, (1R,8S)-3 (1S,8R)-4 and (1R,8S)-7], through asymmetric acylation of (±)-4 (E > 100) or enantioselective hydrolysis (...

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Main Authors: Enikő Forró, Loránd Kiss, Judit Árva, Ferenc Fülöp
Format: Article
Language:English
Published: MDPI AG 2017-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/22/12/2211
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spelling doaj-0f8fb8b09884403f809efe1a9af8d1c72020-11-24T21:08:42ZengMDPI AGMolecules1420-30492017-12-012212221110.3390/molecules22122211molecules22122211Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam EnantiomersEnikő Forró0Loránd Kiss1Judit Árva2Ferenc Fülöp3Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, HungaryEfficient enzymatic resolutions are reported for the preparation of new eight-membered ring-fused enantiomeric β-amino acids [(1R,2S)-9 and (1S,2R)-9] and β-lactams [(1S,8R)-3, (1R,8S)-3 (1S,8R)-4 and (1R,8S)-7], through asymmetric acylation of (±)-4 (E > 100) or enantioselective hydrolysis (E > 200) of the corresponding inactivated (±)-3 or activated (±)-4 β-lactams, catalyzed by PSIM or CAL-B in an organic solvent. CAL-B-catalyzed ring cleavage of (±)-6 (E > 200) resulted in the unreacted (1S,8R)-6, potential intermediate for the synthesis of enantiomeric anatoxin-a. The best strategies, in view of E, reaction rate and product yields, which underline the importance of substrate engineering, are highlighted.https://www.mdpi.com/1420-3049/22/12/2211anatoxin-aβ-Amino acidenzyme catalysisβ-Lactamtraceless activating group
collection DOAJ
language English
format Article
sources DOAJ
author Enikő Forró
Loránd Kiss
Judit Árva
Ferenc Fülöp
spellingShingle Enikő Forró
Loránd Kiss
Judit Árva
Ferenc Fülöp
Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers
Molecules
anatoxin-a
β-Amino acid
enzyme catalysis
β-Lactam
traceless activating group
author_facet Enikő Forró
Loránd Kiss
Judit Árva
Ferenc Fülöp
author_sort Enikő Forró
title Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers
title_short Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers
title_full Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers
title_fullStr Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers
title_full_unstemmed Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers
title_sort efficient enzymatic routes for the synthesis of new eight-membered cyclic β-amino acid and β-lactam enantiomers
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2017-12-01
description Efficient enzymatic resolutions are reported for the preparation of new eight-membered ring-fused enantiomeric β-amino acids [(1R,2S)-9 and (1S,2R)-9] and β-lactams [(1S,8R)-3, (1R,8S)-3 (1S,8R)-4 and (1R,8S)-7], through asymmetric acylation of (±)-4 (E > 100) or enantioselective hydrolysis (E > 200) of the corresponding inactivated (±)-3 or activated (±)-4 β-lactams, catalyzed by PSIM or CAL-B in an organic solvent. CAL-B-catalyzed ring cleavage of (±)-6 (E > 200) resulted in the unreacted (1S,8R)-6, potential intermediate for the synthesis of enantiomeric anatoxin-a. The best strategies, in view of E, reaction rate and product yields, which underline the importance of substrate engineering, are highlighted.
topic anatoxin-a
β-Amino acid
enzyme catalysis
β-Lactam
traceless activating group
url https://www.mdpi.com/1420-3049/22/12/2211
work_keys_str_mv AT enikoforro efficientenzymaticroutesforthesynthesisofneweightmemberedcyclicbaminoacidandblactamenantiomers
AT lorandkiss efficientenzymaticroutesforthesynthesisofneweightmemberedcyclicbaminoacidandblactamenantiomers
AT juditarva efficientenzymaticroutesforthesynthesisofneweightmemberedcyclicbaminoacidandblactamenantiomers
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