Enantioselective synthesis of calcium channel blockers of the diltiazem group

Diltiazem Synthesis, Microbial Asymmetric Reduction

“…1 and 2, is a typical calcium channel blocker and is used clinically as an effective antianginal and antihypertensive agent in more than 100 countries (1). Many methods have been investigated for the synthesis of this optically active medicine (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). On a commercial basis, the standard process of nine chemical synthetic steps had been used for a long time.…”

Synthesis of optically active 1,5-benzothiazepines

“…The first synthesis of (+)-diltiazem was achieved by Inoue et al 44 Utilization of optically active 3-phenylglycidates have been published by several research groups. [45][46][47][48] Racemic nitrocarboxylic acid 49 or aminocarboxylic acid 50 intermediates were optically resolved via distereomeric salt formation. Optically active intermediates used for the synthesis of the diltiazem have also been prepared by enzyme-catalyzed resolution.…”

Corrigendum: β‐Enaminonitriles in Heterocyclic Synthesis: Synthesis of New 1,4‐Dihydropyridine, Tetrahydropyridine, Nicotinonitrile and Aminopyrazole Derivatives

“…A number of papers and patents concerning the importance of b-enaminonitriles in the synthesis of biologically active compounds such as; dihydropyridines analogous to nifedipine and amlodipine which considered as a potential calcium channel blockers in the treatment of angina and hypertension. [1][2][3][4][5] Pyridine derivatives occur in numerous natural products which are of fundamental importance to living systems (e.g., nicotinamide adenine dinucleotide (NAD)). They display interesting physiological activities with attractive applications as pharmaceuticals and agro-chemicals, as well as general synthetic building blocks.…”