Phorboxazole synthetic studies. 1. Construction of a C(3-19) subtarget exploiting an extension of the Petasis-Ferrier rearrangement.
[formula: see text] In this, the first of two letters, we outline our overall strategy for the total synthesis of phorboxazoles A (1) and B (2), rare oxazole-containing macrolides possessing extraordinary antimitotic activity, and describe the assembly of a C(3-19) subtarget (-)-5 for the total synthesis of phorboxazole A. The synthesis of (-)-5 was achieved in 15 linear steps (12% overall yield), exploiting a modification of the Petasis-Ferrier rearrangement to construct the C(11-15) cis-tetrahydropyran. Dimethylaluminum chloride (Me2AlCl) proved to be the Lewis acid of choice for the Petasis-Ferrier rearrangement.
Smith
A B
AB
Department of Chemistry, University of Pennsylvania, Philadelphia 19104, USA. smithab@sas.upenn.edu
Verhoest
P R
PR
Minbiole
K P
KP
Lim
J J
JJ
D000143:Acids / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D010080:Oxazoles / Q000138:chemical synthesis*; D010084:Oxidation-Reduction
D000143:Acids; D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A