Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement.
A highly convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include: modified Petasis-Ferrier rearrangements for assembly of both the C(11-15) and C(22-26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional oxazole linchpin; and Stille coupling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The longest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with an overall yield of 3%.
Smith
A B
AB
Department of Chemistry, Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Minbiole
K P
KP
Verhoest
P R
PR
Schelhaas
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D010080:Oxazoles / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A