Diphenic Acid as a General Conformational Lock in the Design of Bihelical Structures

摘要

The bihelical(figure of "infinity")topology was examined from vantages of design,crystal structures,chirality,circular dichroism(CD)studies and molecular-orbital calculations.The minimalistic design envisaged the se quential linking of cystine to the anchor diphenic acid,which proved to be a general conformational lock.The bihelical compound 4 was obtained in two steps from diphenic anhydride 1 and cystine di-OMe.The chirality of 4 arises largely from the L-cystine.The bihelical compound 5 obtained from D-cystine di-OMe was found,by X-ray crystallography,CD studies,and optical rotation,to be 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 analogue cystamine,had a "U"-shaped conformation held together by intramolecular hydrogen bonds.Analysis of 4 and 5 show that the pairs of nine-membered beta-turn-like constructs made compact through hy drogen bonding with DMSO hold the key for the bihelical conformation.An other factor is the need for the pres ence of a ligand at the C alpha position.The absence of this,as in 8,allows major flexibility in the torsional angles around this critical region,promoting flexible alternatives.The CD analysis of 4,confirmed to be bihelical by X-ray crystallography,showed a typical negative band at about 210 A attribut-ed to the beta-turn-like motif,and in the positive-band region a peak at about 227 A,generally related to the twist of the biphenyl unit.The cystamine ana logue 8,which showed a "U"-type structure,presented a CD spectrum with no typical features.The total energy,derived from theoretical calcu lations by using the X-ray structure data,support the bihelical structure for 4 and a "U"-shaped one for 8.The lim ited utility of such calculations was tested with composite 9.Composite 9.in which the anchor diphenic acid is linked to cystamine on the one hand and to cystine on the other,showed a CD spectrum similar to that of 4,and this coupled with molecular-orbital cal culations,using data from 4 and 8,pre dict a bihelical structure for this com pound.