Noniterative approach to the total asymmetric synthesis of 15-carbon polyketides and analogs with high stereodiversity
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-1,3,5,7,9,1 1,13,15-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: polyene macrolide antibiotics ; delta-valerolactones ; enantioselectivesynthesis ; stereoselective-synthesis ; beta-hydroxyketones ; building-blocks ; aldol reactions ; amphotericin-b ; lactone moiety ; mevinic acid
Record created on 2005-11-09, modified on 2016-08-08