Total synthesis of (+)-chloriolide.
(+)-Chloriolide, a metabolite of the ascomycete Chloridium virescens var. chlamydosporum, was synthesized in 16 linear steps from cellulose as a source of a levoglucosenone that contributed the (Z)-alkene and the R stereocenter. The attachment of a spacer derived from l-lactate gave an ω-hydroxyacetal which was added to the phosphorus ylide Ph3PCCO. The resulting ester ylide was treated with hydrochloric acid to liberate the hemiacetal shown. Addition of sodium hydroxide regenerated the corresponding ylide, which underwent a spontaneous intramolecular Wittig olefination to afford (+)-chloriolide in 65% yield without the necessity of high-dilution conditions. This is the third synthesis of (+)-chloriolide and the first one ever of a macrolide by a ring-closing Wittig olefination of a stabilized phosphorus ylide bearing an ω-hemiacetal. Our synthetic sample exhibited moderate cytotoxicity against cancer cells but no antimicrobial activity against Staphylococcus aureus.
Organic Chemistry Laboratory, University of Bayreuth , 95440 Bayreuth, Germany.
Michael
M
Ostermeier
Rainer
R
Schobert
D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D018942:Macrolides; C510706:chloriolide