[Discovery of cis-preference of aromatic N-methylamides and its application to molecular constructions].

Aromatic secondary amides such as benzanilide (1) exist in a trans-amide form both in the crystal and in the solution, whereas N-methylbenzanilide (2) exists in cis form in the crystal, and predominantly in a cis form in the solution. Similar cis conformational preferences were observed in aromatic N,N'-dimethylated ureas and guanidines, in which two aromatic rings are located face to face. The cis preferences of N-methylated amides, ureas and guanidines could be utilized to construct interesting aromatic architecture. N,N',N"-Trimethyl-N,N',N"-triphenyl-1,3,5-benzenetricarboxamide (20) and a cyclic triamide (24) have crystal structures in which three N-phenyl groups direct to the same orientation (syn conformation). 1,2-Bis(N-benzoyl-N-methylamino)benzene (22), which have no fixed asymmetric center, afforded chiral crystals by simple recrystallization. Furthermore, aromatic multi-layered structures could be built and applied to obtain aromatic molecules which have potent DNA-binding ability.

Synthesis and coupling reactions of alpha,alpha-dialkylated amino acids with nucleobase side chains.

Several di- and tripeptides containing protected purine (adenine) and pyrimidine (thymine) residues on their side chains were synthesized. The parent amino acids alpha, alpha-dialkylated in a symmetrical manner. An effective coupling procedure was developed for these sterically hindered amino acids: the fluoren-9-ylmethyloxycarbonyl-protected amino acid was dehydrated to its oxazolinone form, which was coupled in good yields with amino esters in hot tetrachloroethane.

[Stereochemistry of benzanilides and N-methylbenzanilides].

Conformations of benzanilide , N-methylbenzanilide and those with a methyl group(s) ortho to the amide bond in solution and in the crystal have been studied. N-Methylbenzanilide exists in cis-amide (E) form in the crystal. In CDCl3 solution, cis-amide form is also predominant (99%), while benzanilide exists in trans-amide (Z) form in the crystal and in solution. In the crystal, all the methyl-substituted benzanilides exist in trans-amide conformation and the introduction of an ortho-methyl group(s) makes the interplanar angles of the aromatic rings and the amide group (Aramide) larger. N-Methylbenzanilides exist in cis form in the crystal except the compound which has four methyl groups ortho to the amide bond. For the N-methylbenzanilides, the effects of introduction of one or two ortho-methyl groups on the dihedral angles of Ar-amide are smaller than that for the secondary benzanilides. In solution, benzanilides exist exclusively in trans conformation except for the compound 12 which has a minor cis conformer (3%) in CDCl3, whereas N-methylbenzanilides exist in equilibrium between the major cis-form and the minor trans-form. The tetramethyl derivative exists in trans conformation in solution as observed in the crystal. For N-methylbenzanilides, an introduction of a methyl group(s) ortho to the amide bond seems to destabilize the cis-amide conformation in solution, resulting in an increased ratio of the trans-amide conformation.