A practical synthesis for the core structure of a family of selective prostaglandin D2 receptor antagonists.
A convergent synthesis was developed for the production of the core structure of prostaglandin D(2) receptor antagonists for the treatment of allergic rhinitis. The key steps in this synthesis were a highly diastereoselective alkylation of (+)-nopinone, a chemo- and stereoselective reduction of an oxime to an amine, and a well-controlled reduction of an aminoalkyne to a (Z)-olefin.
Campos
Kevin R
KR
Department of Process Research, Merck Research Laboratories, P.O. Box, 2000, RY800-B267, Rahway, New Jersey 07065-0900, USA. kevin_campos@merck.com
Journet
Michel
M
Cai
Dongwei
D
Kowal
Jason J
JJ
Lee
Sandra
S
Larsen
Robert D
RD
Reider
Paul J
PJ
D000478:Alkylation; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003516:Cycloparaffins / Q000138:chemical synthesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*; D013237:Stereoisomerism; D013696:Temperature
D001952:Bridged-Ring Compounds; D003516:Cycloparaffins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C476481:nopinone; C036293:prostaglandin D2 receptor