ORGN 593

There are several methods for determination of relative and absolute stereochemistry in acyclic 1,2- and 1,3-diols and related polyols, however, non-empirical methods for 1,5-diols or polyols with OH groups are notably absent. Natural products structures (e.g. polyketides) that contain separated multiple OH groups isolated by intervening chains of 3 or more methylene groups are effectively insulated by distance. Current methods for determination of configuration of secondary OH groups at remote centers (Mosher's ester analysis, J based analysis) are critically dependent upon high-field NMR and signal dispersion. The recently isolated polyketide caylobalide A (1) from the cyanobacterium Lyngbya majuscula presents an interesting challenge in stereochemical assignment due to the presence of five stereogenic centers within a pentad of repeating 1,5 diols. We have developed an approach to configurational assignment of 1,n-diols (n=5,7,9) that relies on exciton coupling in circular dichroism (CD). Model 1,n-diols were prepared by enantioselective synthesis, and the diols derivatized with 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (TPP, l_max 419 nm, e 550,000). CD measurements of the resulting O-TPP esters in isotropic solvents (eg. MeOH, CH₃CN) gave no signal but strong bisignate CD signals were observed in non-isotropic media which could be correlated with the relative and absolute configuration of the diols. Application of this approach to determination of remote centers in natural products will be presented.