A one-pot enantioselective route to N-unprotected 2,3-dihydro-1,5-benzothiazepinones, by an organocatalyzed sulfa-Michael reaction of readily available a,b-unsaturated N-acyl pyrazoles with 2-aminothiophenols followed by silica-gel-catalyzed lactamization, has been developed. The method proceeds under mild conditions at room temperature and it requires only 1 mol% catalyst loading, to give 2-aryl/alkyl-substituted 1,5-benzothiazepines in generally good to excellent yields and enantioselectivities. The process, used for a short synthesis of antidepressant drug (R)-thiazesim, represents the first method to access enantioenriched unprotected 1,5-benzothiazepines, which are useful for rapid derivatization in drug discovery.
Catalytic Enantioselective Synthesis of Protecting-Group-Free 1,5-Benzothiazepines
MENINNO, SARAMethodology
;LATTANZI, Alessandra
Conceptualization
;Volpe, ChiaraMethodology
2017-01-01
Abstract
A one-pot enantioselective route to N-unprotected 2,3-dihydro-1,5-benzothiazepinones, by an organocatalyzed sulfa-Michael reaction of readily available a,b-unsaturated N-acyl pyrazoles with 2-aminothiophenols followed by silica-gel-catalyzed lactamization, has been developed. The method proceeds under mild conditions at room temperature and it requires only 1 mol% catalyst loading, to give 2-aryl/alkyl-substituted 1,5-benzothiazepines in generally good to excellent yields and enantioselectivities. The process, used for a short synthesis of antidepressant drug (R)-thiazesim, represents the first method to access enantioenriched unprotected 1,5-benzothiazepines, which are useful for rapid derivatization in drug discovery.File | Dimensione | Formato | |
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Enantioselective synthesis of benzothiazepines manuscript_watermarked.pdf
Open Access dal 23/03/2018
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