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Chemoenzymatic Synthesis of Optically Active cis ‐ and trans ‐2‐(1 H ‐Imidazol‐1‐yl)cycloalkanamines
Author(s) -
AlatorreSantamaría Sergio,
GotorFernández Vicente,
Gotor Vicente
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201001299
Subject(s) - enantiopure drug , candida antarctica , chemistry , biocatalysis , optically active , lipase , mitsunobu reaction , amine gas treating , stereochemistry , kinetic resolution , racemic mixture , active site , enzyme , enantiomer , enantioselective synthesis , combinatorial chemistry , organic chemistry , catalysis , reaction mechanism
Abstract The preparation of enantiopure 2‐(1 H ‐imidazol‐1‐yl)cycloalkanamines has been studied by independent chemoenzymatic approaches. We first explored a route involving the enzymatic resolution of racemic cycloalkanol analogs for the preparation of the corresponding optically active amines by diverse substitution methodologies including (a) the formation of a mesylated intermediate that could be later substituted by an amine group and (b) the combination of Mitsunobu inversion of the hydroxy group followed by a deprotection step. In order to overcome low isolated yields of the desired optically active amines, racemic‐ trans ‐2‐(1 H ‐imidazol‐1‐yl)cycloalkanamines were prepared, and their lipase‐catalyzed enzymatic resolutions were studied. These efforts revealed that lipase from Candida antarctica type B was an efficient biocatalyst. A combination of both chemoenzymatic methodologies has allowed us to obtain the four different enantiopure cis ‐ and trans ‐(1 H ‐imidazol‐1‐yl)cycloalkanamine isomers.