Stereocontrolled syntheses of epimeric 3-aryl-6-phenyl-1-oxa-7-azaspiro(4.5)decane NK-1 receptor antagonist precursors.
[structure: see text]. Complementary stereoselective syntheses of individual C3 epimers of the NK-1 receptor antagonist precursor 1 have been developed. Both diastereomers were derived from the common intermediate 3; introduction of the 3S stereocenter in 1a was achieved through hydrogenation of an arylated dihydrofuran, whereas the corresponding stereogenic center in 1b was installed using a stereo- and regioselective alkene hydroarylation.
Kulagowski
J J
JJ
Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK. janusz_kulagowski@merck.com
Curtis
N R
NR
Swain
C J
CJ
Williams
B J
BJ
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
C426927:3-aryl-6-phenyl-1-oxa-7-azaspiro(4.5)decane; D001372:Aza Compounds; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds