A second-generation total synthesis of (+)-phorboxazole A.
A highly convergent second-generation synthesis of (+)-phorboxazole A has been achieved. Highlights of the synthetic approach include improved Petasis-Ferrier union/rearrangement conditions on a scale to assemble multigram quantities of the C(11-15) and C(22-26) cis-tetrahydropyrans inscribed with the phorboxazole architecture, a convenient method to prepare E- and Z-vinyl bromides from TMS-protected alkynes utilizing radical isomerization of Z-vinylsilanes, and a convergent late-stage Stille union to couple a fully elaborated C(1-28) macrocyclic iodide with a C(29-46) oxazole stannane side chain to establish the complete phorboxazole skeleton. The synthesis, achieved with a longest linear sequence of 24 steps, proceeded in 4.6% overall yield.
Smith
Amos B
AB
Department of Chemistry, The Penn Center for Molecular Discovery, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Razler
Thomas M
TM
Ciavarri
Jeffrey P
JP
Hirose
Tomoyasu
T
Ishikawa
Tomoyasu
T
Meis
Regina M
RM
D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A