Pure Appl. Chem., 2005, Vol. 77, No. 1, pp. 131-137
doi:10.1351/pac200577010131
Noniterative approach to the total asymmetric synthesis of 15-carbon polyketides and analogs with high stereodiversity*
Pierre Vogel‡, Sandrine Gerber-Lemaire, Ana T. Carmona, Kai Torsten Meilert, and Marc-Etienne Schwenter
Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne (EPFL), BCH, CH-1015 Lausanne-Dorigny, Switzerland
Abstract:
Starting from inexpensive furan and furfuryl alcohol, a noniterative approach to the synthesis of pentadeca-1,3,5,7,9,11,13,15-octols and their derivatives has been developed. The method relies upon the double [4+3]-cycloaddition of 1,1,3-trichloro-2-oxylallyl cation with 2,2'-methylenedifuran and conversion of the adducts into meso and (±)-threo-1,1'-methylenebis (cis- and trans-4,6-dihydroxycyclohept-1-ene) derivatives. The latter undergo oxidative cleavage of their alkene moieties, generating 5-hydroxy-7-oxoaldehydes that are reduced diastereoselectively into either syn or anti-5,7-diols. Asymmetry is realized using either chiral desymmetrization with Sharpless asymmetric dihydroxylation or by kinetic resolution of polyols using lipase-catalyzed acetylations. All of the possible stereomeric pentadeca-1,3,5,7,9,11,13,15-octols and derivatives can be obtained with high stereoselectivity applying simple operations, thus demonstrating the high stereodiversity of this new, noniterative approach to the asymmetric synthesis of long-chain polyketides.
Keywords: 2,2'-methylenedifuran; 8-oxabicyclo[3.2.1]oct-6-en-3-one; asymmetric dihydroxylation; asymmetric synthesis; desymmetrization; lipase-catalyzed acetylation; long-chain polyketides; stereodiversity.
*Paper based on a presentation at the 24th International Symposium on the Chemistry of Natural Products and the 4th International Congress on Biodiversity, held jointly in Delhi, India, 26-31 January 2004. Other presentations are published in this issue, pp. 1-344.