Planta Med 2008; 74 - SL69
DOI: 10.1055/s-0028-1083949

Configuration of natural products: Liposomal circular dichroism (LCD) for acyclic stereocenters

TF Molinski 1, 2, DS Dalisay 1, BI Morinaka 1, T Quach 1
  • 1Department of Chemistry and Biochemistry, UC San Diego, CA 92093–0358, USA
  • 2Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, CA 92093–0358, USA

Circular dichroism (CD) is a powerful tool for configurational analysis of organic molecules [1] that exploits asymmetric perturbation of chromophores (UV-vis) or interaction between chromophores (exciton coupling)[2]. Its limitations are felt in acyclic molecules where stereogenic centers lie remote from the chromophore and the effects become weak or disappear entirely. Nevertheless, even weak effects can be used together with synthetic models to assign acyclic, remote stereoelements [3]. Recently, we've developed CD methods [4,5] that exploit the use of liposomes for alignment of long-chain segments of natural products that allow assignments of relative and absolute configurations of 1,n-diols (n=5, 7, 9...) often found in polyketides. Now, we present new results that show how asymmetric perturbation of a single chromophore can be amplified to provide stereochemical information at remote unfunctionalized stereocenters (e.g. methyl-branched centers) and demonstrate its application to solutions of some outstanding stereochemical problems. The technique appears to have general applicability, particularly in polyketide natural products.

Acknowledgements: We gratefully acknowledge funding from the National Institutes of Health (USA) (AI39987, CA122256)

References: 1. Nakanishi, K., Berova, N., Woody, R. W. (1994) Circular Dichroism: Principles and Applications. VCH. New York.

2. Harada, N., Nakanishi, K. (1983) Circular Dichroic Spectroscopy: Exciton Coupling in Organic Stereochemistry. University Science Books. Mill Valley, CA

3. (a) Skepper, C. K. et al (2007)J. Am. Chem. Soc. 129:4150–4151. (b) Morinaka, B. I. et al. (2007) Org. Lett. 9:1975–78. (c) Morinaka, B. I. et al. (2007) Org. Lett. 9:5219–22.

4. MacMillan, J. B., Molinski, T. F. (2004)J. Am. Chem. Soc. 126:9944–45

5. MacMillan, J. B., Molinski, T. F. (2004) Angew. Chem. Intl. Ed. 43:5946:51

6. Dalsay, D. S. et al. (2008), submitted.