Synthesis and X-ray Structure of the Chiral, Polydentate Cation Binder N--L-methionyl>histamine

Article abstract of DOI:10.1021/jo00019a027

A synthetic route has been developed to obtain N--L-methionyl>histamine, optically pure (α²⁰ = -8.13 deg/L mol^-1 dm^-1), from a sequence of reactions involving L-methionine, histamine, and 5-methyl-2-thiophenecarbaldehyde.The described procedure affords gram quantities in an overall yield of 40percent, without the need of any chromatographic techniques.Moreover, the removal of the well-known tert-butyloxycarbonyl amino-protection group (BOC) with gaseous hydrochloric acid, in the present synthesis, had considerable advantages compared with the commonly applied trifluoroacetic acid method.The structure of N--L-methionyl>histamine in the solid has been determined by X-ray diffraction techniques.C16H22N4OS2 crystallizes in the monoclinic space group P2₁, with a = 5.233(1), b = 9.556(1), and c = 17.919(1) Angstroem; β = 98.32(1) deg; and Z = 2.Noteworthy aspects of the tertiary structure of the molecule are the fact that it is almost flat, the three arms connected to methionine-C_a, being the (thienylmethylidene)amino moiety, the "imidazole-amide" fragment, and the methionine side chain, spread out. ?-Conjugation causes the (thienylmethylidene)amino moiety to have a planar s-cis conformation, and the methionine side chain's all-trans conformation is due to vicinal interactions.The gauche conformation of the "imidazole-amide" does not have a clear origin, but is no artifact of the solid state.Intra- and intermolecular hydrogen bonds are prominently present, the former determining the relative orientations of the aforementioned arms and the latter linking the title molecules into two-dimensional, sheetlike entities.