Diphenic acid as a general conformation lock in the design of bihelical structures

摘要

The bihelical (figure of “∞”) topology has been examined from vantages of design, crystal structures, chirality, CD studies and molecular orbital calculations. The minimalistic design envisaged the sequential linking of cystine to the anchor diphenic acid, which proved to be a general conformation lock.The bihelical compound >4 was obtained in two steps from diphenic anhydride >1 and cystine di-OMe. The chirality of >4 largely arises from the L-cystine. The bihelical compound >5 from D-cystine di-OMe was found to be, by X-ray crystallography, CD studies, and optical rotation the perfect mirror image of >4 prepared from L-cystine. The crystal structure of prototype >8, prepared by protocols used for >4, from the achiral cystine analog, cystamine had a “U” shaped conformation held by intramolecular hydrogen bonds.Analyses of >4 and >5 show that the pairs of nine-membered β-turn like constructs made compact with hydrogen bonding with DMSO holds the key for the bihelical conformation. Another factor is the need for the presence of a ligand at the Cα position. The absence of this as in >8 allows major flexibility in the torsional angles around this critical region, promoting flexible alternatives.The CD of >4, confirmed bihelical by X-ray, showed a typical negative band at ~210 Å attributed to the β-turn like motif and in the positive band region a peak ~227 Å, generally related to the twist of the biphenyl unit. The cystamine analog >8, which showed a “U” type structure, presented a CD with no typical features.The total energy, derived from theoretical calculations using the X-ray structure data, support the bihelical structure for >4 and a “U” shaped one for >8. The limited utility of such calculations has been tested with composite >9.Composite >9 where the anchor diphenic acid is linked to cystamine on the one hand and cystine on the other showed a CD similar to that of >4, and this coupled with molecular orbital calculations, using data from >4 and >8, predict a bihelical structure for this compound.