Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge Phorbas sp.
A convergent total synthesis of phorboxazole A (1a), from the C(3-19), C(20-27) and C(33-46) fragments 5, 4 and 91, respectively, concentrating on stereocontrolled formation of the bonds at C(2-3), C(19-20) and C(27-28), is described. Although a coupling reaction between a macrolide ketone and the side chain substituted sulfone, at C(27-28) was not successful, a Wadsworth-Emmons olefination involving the oxane methyl ketone 4 and an oxazole produced the oxane 90 which was next coupled to 91 leading to the C(20-46) unit 100. A further coupling of 100 to 71c at C(19-20) then led to 105, ultimately, and the synthesis was completed by a macrocyclisation reaction from 105, at the C(2-3) alkene bond, followed by deprotection of 106.
Pattenden
Gerald
G
School of Chemistry, The University of Nottingham, University Park, Nottingham, UK NG7 2RD. gp@nottingham.ac.uk
González
Miguel A
MA
Little
Paul B
PB
Millan
David S
DS
Plowright
Alleyn T
AT
Tornos
James A
JA
Ye
Tao
T
D000818:Animals; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A