Solving challenging bioorganic problems by exciton coupled CD

Nina Berova, Babak Borhan, J. G. Dong, J. Guo, X. Huang, Elena Karnaukhova, A. Kawamura, Jihong Lou, Stefan Matile, K. Nakanishi, B. Rickman, J. Su (+2 others)
1998 Pure and Applied Chemistry  
Determination of molecular chirality is becoming increasingly important due to the sophistication in mode of action studies of biological reactions and the importance of chiral drugs. The exciton coupled CD, based on through space coupling, is a versatile microscale method with superb sensitivity that can be applied to a variety of problems including biopolymers and clusters in lipids. Applications of the exciton coupled CD method to the following problems exemplify its versatility. Quaternary
more » ... tility. Quaternary ammonium salts as chromophores for exciton-coupled CD.1' Exciton coupled circular dichroism is a nonempirical submicrogram scale method for determining absolute configurations and conformations of organic molecules in solution based on the interactions of chromophores which are preexisting in the substrate and/or introduced through derivatizations such as 0or N-acylation.213 However, the method could not be applied to one major group, i.e., tertiary amines which comprise numerous natural products, particularly alkaloids, and synthetic drugs that exhibit conspicuous biological activities. We have succeeded in extending the CD method to quinuclidines (tertiary amines) through quaternary ammonium salt formation, and have applied this new procedure to the important class of hypocholesterolemic quinuclidines. Of the three conformers conceivable for the salt (l), the conformer shown determines the sign of the split Cotton effect (CE). When the phenylbenzyl group is in the north east sector the transition moments ,of the two chromophores are close to being parallel, hence the chirality is negligible; when it is in the north west sector, the distance between the two chromophores is more remote than that depicted, hence the resulting positive bisignate CD will be of smaller amplitude. OMe Acyclic 1,3-polyols with a 1,2-diol terminal.4 Acyclic 1,3-polyols are widely distributed in nature. Particularly 1,2,4-triols are present in numerous antifungal polyene macrolides in various masked forms. Although over 200 polyene macrolides are known, the structures of only about 40 have been determined, while those for which the full stereochemistry has been elucidated are less than ten. In order to develop a general chiroptical method for structure determination of acyclic 1,3-polyols, we have combined a divergent synthetic approach with CD to prepare all possible stereoisomers of 1,2,4-triols, 1,2,4,6tetrols and 1,2,4,6,8-pentols. The current set of reference polyols should be useful for setting up reference CD libraries and for model studies leading to a general method for configurational assignment of acyclic polyols. CD curves of 1,2-diols, 1,2,4-triols, and 1,2,4,6-tetrols with differing stereochemistries have been published earlier.5 3. Synthesis of cyclic mixed polyols6 and acyclic pentol structure of two hopanoids.7 The synthesis of all eight configurational isomers of acyclic 1,2,3,4,6-pentols belonging to the 2R enantiomeric series has been carried out, and the side-chain configurations of two bacteriohopanoids (2) and (3) have been established by microgram scale derivatization and CD.
doi:10.1351/pac199870020377 fatcat:pwr5lt46anbfvebuog5xxhgw4a