A stereoselective synthesis of BMS-262084, an azetidinone-based tryptase inhibitor.
A highly stereoselective synthesis of the novel tryptase inhibitor BMS-262084 was developed. Key to this synthesis was the discovery and development of a highly diastereoselective demethoxycarbonylation of diester 12 to form the trans-azetidinone 13. BMS-262084 was prepared in 10 steps from D-ornithine in 30% overall yield.
Qian
Xinhua
X
Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, 1 Squibb Drive, P.O. Box 191, New Brunswick, NJ 08903-0191, USA. xinhua.qian@bms.com
Zheng
Bin
B
Burke
Brian
B
Saindane
Manohar T
MT
Kronenthal
David R
DR
D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis; D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry*; D009952:Ornithine / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis*; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism; D053802:Tryptases
C116379:2-azetidinone; D018927:Anti-Asthmatic Agents; D001384:Azetidines; C467955:BMS-262084; D010879:Piperazines; D015842:Serine Proteinase Inhibitors; D009952:Ornithine; D012697:Serine Endopeptidases; D053802:Tryptases