Chemoenzymatic preparation of optically active trans-cyclohexane-1,2-diamine derivatives: an efficient synthesis of the analgesic U-(-)-50,488.
Stereoespecific syntheses of (+/-)-trans-N,N-cyclohexane-1,2-diamines ((+/-)-4 a-g) were carried out from the corresponding (+/-)-trans-N,N-dialkylaminocyclohexanols by successive treatment with mesyl chloride and aqueous ammonia. The stereochemical outcome indicates the formation of a meso-aziridinium ion intermediate. Kinetic resolutions of diamines (+/-)-4 were efficiently accomplished in aminolysis reactions catalyzed by lipase B from Candida antarctica with ethyl acetate as the solvent and acyl donor. Acetamides and the remaining diamines, isolated as the benzyloxycarbonyl derivatives, were obtained with very high ee values (92-99%). One of the carbamates was used as a precursor of the analgesic U-(-)-50,488.
González-Sabín
Javier
J
Departamento de Química Orgánica e Inorgánica, Facultad de Química, Universidad de Oviedo, Oviedo, Spain.
Gotor
Vicente
V
Rebolledo
Francisca
F
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D000588:Amines / Q000737:chemistry; D000700:Analgesics / Q000737:chemistry* / Q000378:metabolism*; D003510:Cyclohexanes / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry*; D004800:Enzymes, Immobilized / Q000378:metabolism*; D005656:Fungal Proteins; D008049:Lipase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D000588:Amines; D000700:Analgesics; D003510:Cyclohexanes; D003959:Diamines; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D008049:Lipase; C431349:lipase B, Candida antarctica