Total synthesis of sporolide B and 9-epi-sporolide B.
The total synthesis of the structurally unique secondary metabolite sporolide B (1b) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37 and 75) that underwent exquisite intramolecular [4+2] cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b. The requisite indene o-quinone precursor 75 was synthesized through a ruthenium-catalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol and a chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed [2+2+2] cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus.
Nicolaou
K C
KC
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Wang
Jianhua
J
Tang
Yefeng
Y
Botta
Lorenzo
L
D000480:Alkynes / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000480:Alkynes; D018942:Macrolides; C509191:sporolide A