title: Synthetic Studies of Antitumor Macrolide Rhizoxin: Stereoselective Syntheses of the C(1)-C(9) and C(12)-C(26) Subunits.
abstract: A triply convergent synthetic approach which culminates in the enantioselective syntheses of the C(1)-C(9) and C(12)-C(26) subunits of the macrolide antitumor agent rhizoxin is described. The central C(12)-C(20) subunit 4 has been prepared efficiently via diastereoselective enzymatic acetate hydrolysis of 15 with porcine pancreatic lipase, a chelation-controlled Ireland-Claisen rearrangement (10 --> 12) combined with kinetic bromolactonization (12 --> 14), and Mitsunobu inversion (23 --> 26) to introduce the three contiguous C(15)-C(17) stereocenters. Formation of the C(18)-C(19) trisubstituted (E)-olefin was achieved by a stereoselective Horner-Wadsworth-Emmons reaction. The central segment 4 and the oxazole chromophore side chain 3 were coupled using another highly stereoselective Horner-Wadsworth-Emmons reaction. Two different lactone subunits [C(1)-C(9) segment 5 and C(3)-C(10) segment 47] were also prepared, employing a thermodynamically controlled diastereotopic group differentiation tactic for establishing the C(5) stereochemistry.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, and Department of Chemical Sciences, Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
authors.forename: Steven D.
authors.initials: SD
authors.lastname: Burke
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Joseph R.
authors.initials: JR
authors.lastname: Lennox
authors.forename: Andrew P.
authors.initials: AP
authors.lastname: Mongin