Total synthesis of enigmazole A from Cinachyrella enigmatica. Bidirectional bond constructions with an ambident 2,4-disubstituted oxazole synthon.
The first total synthesis of the cytotoxic marine macrolide enigmazole A has been completed in 22 steps (longest linear sequence). The sensitive, densely functionalized 2,4-disubstituted oxazole fragment was constructed using an efficient Negishi-type coupling of an oxazol-2-ylzinc reagent formed directly from the parent ethyl 2-iodooxazole-4-carboxylate by zinc insertion. Other key steps include a hetero-Diels-Alder cycloaddition to form the central embedded pyran ring, a Wittig reaction to unite Eastern and Western hemispheres, and a ring size-selective Keck macrolactonization.
Skepper
Colin K
CK
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive MC0358, La Jolla, California 92093, USA.
Quach
Tim
T
Molinski
Tadeusz F
TF
D000818:Animals; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry*
D003603:Cytotoxins; D018942:Macrolides; D009943:Organophosphorus Compounds; D010080:Oxazoles; C553539:enigmazole A