A new synthesis of cytoxazone and its diastereomers provides key initial SAR information.
A short, enantioselective, and diastereoselective synthesis of cytoxazone, a Th2-selective immunomodulator from Streptomyces, is described. The route was readily adapted to the synthesis of the three other stereoisomers of natural cytoxazone. Evaluation of these compounds revealed that the stereochemical configuration of the oxazolidinone ring did not influence their biological activity.
Carter
Percy H
PH
Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. percy.carter@bms.com
LaPorte
Jacob R
JR
Scherle
Peggy A
PA
Decicco
Carl P
CP
D000215:Acylation; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D010080:Oxazoles; D011043:Pokeweed Mitogens; D016753:Interleukin-10; C117832:cytoxazone