Asymmetric synthesis of (+)-L-733, 060 and (+)-CP-99, 994 based on a new chiral 3-piperidinol synthon.
[reaction: see text] Selective and potent neurokinin substance P receptor antagonists (+)-L-733, 060 (1) and (+)-CP-99, 994 (2) have been synthesized starting from a new (3S)-piperidinol synthon derived from l-glutamic acid. The methods featured a C-2 regioselective reduction of glutarimide (9), Lewis acid-promoted Si to C-2 phenyl group migration of 10, and stereoselective reduction of acetylated oxime 19 as the key steps.
Huang
Pei-Qiang
PQ
Department of Chemistry, Xiamen University, Xiamen, Fujian 361005, P. R. China. pqhuang@xmu.edu.cn
Liu
Liang-Xian
LX
Wei
Bang-Guo
BG
Ruan
Yuan-Ping
YP
D000107:Acetylation; D018698:Glutamic Acid / Q000737:chemistry; D007202:Indicators and Reagents; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism
D007202:Indicators and Reagents; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D018698:Glutamic Acid