Synthesis of erythromycin derivatives via the olefin cross-metathesis reaction.
Olefin cross metathesis (CM) was applied to the synthesis of 6-O-substituted erythromycin derivatives. The reactions were catalyzed by transition metal alkylidene complexes, particularly bis(tricyclohexylphosphine)benzylidine ruthenium (IV) dichloride (Grubbs' first-generation catalyst). This approach allowed for the elaboration of the 6-O-allyl group of highly functionalized macrolides at various stages of the synthetic sequence, affording 6-O-3-aryl-propenyl products with excellent E-selectivity. Little or no self-dimerization of the reacting components was found in the crude mixtures. Preliminary kinetic data accounts for the observed cross-selectivity based on substrate reactivity and steric factors.
Hsu
Margaret C
MC
Process Chemistry Research and Development, Global Pharmaceutical R&D, Abbott Laboratories, 1401 Sheridan Road, North Chicago, Illinois 60064, USA. margaret.hsu@abbott.com
Junia
Adam J
AJ
Haight
Anthony R
AR
Zhang
Weijiang
W
D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D012428:Ruthenium; D013237:Stereoisomerism
D000475:Alkenes; D009942:Organometallic Compounds; C524958:bis(trichlorohexylphosphine)benzylideneruthenium; D004917:Erythromycin; D012428:Ruthenium