Total synthesis of (-)-zampanolide and questionable existence of (-)-dactylolide as the elusive biosynthetic precursor of (-)-zampanolide in an Okinawan sponge.
A new and concise total synthesis of (-)-zampanolide, (-)-1, and (-)-dactylolide, (-)-2, is described. Synthetic highlights include (i) a mild Horner-Wadsworth-Emmons reaction providing the seco acid, (ii) an unusual stepwise cross-coupling reaction of a 1,1-dibromodiene with inversion of olefin geometry, and (iii) specific O-Michael reaction conditions using catalytic LHMDS with TMEDA for the synthesis of functionalized 2,6-cis-tetrahydropyran. A marine sponge extract was analyzed for the presence of (-)-2 as the biosynthetic precursor of (-)-zampanolide.
Uenishi
Jun'ichi
J
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412 Japan. juenshi@mb.kyoto-phu.ac.jp
Iwamoto
Takuya
T
Tanaka
Junichi
J
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002460:Cell Line; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D011161:Porifera / Q000737:chemistry
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D018942:Macrolides; C451487:dactylolide; C444900:zampanolide