Studies toward the total synthesis of clavulactone.
Synthetic studies directed toward a total synthesis of clavulactone are reported. In light of the analysis made in our previous work, cyclopentane 4a (a key intermediate in the present work) was synthesized through a radical-mediated ring closure of a rationally designed substrate 25. Using HWE reactions, the lower and upper side-chains of 4a were converted into an allyl chloride and an allyl cyanohydrin, respectively. Subsequent treatment of the allyl chloride/cyanohydrin in a highly diluted THF solution with sodium bis(trimethylsiliyl)amide led to intramolecular alkylation and thus completed a major endeavor in synthesizing the dolabellane framework, construction of the eleven-membered ring. SmI(2)-mediated lactonization as a model reaction for the formation of the alpha,beta-unsaturated delta-lactone segment of clavulactone is also described.
Zhu
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State Key laboratory of Bio-organic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
Qiao
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Wu
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Wu
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D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D004224:Diterpenes / Q000138:chemical synthesis*; D005690:Galactose / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis*; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004224:Diterpenes; D007783:Lactones; C438459:clavulactone; C115566:dolabellane; D005690:Galactose