The tripeptide L-alanyl-L-alanyl-L-alanine has been crystallized from a water/dimethylformamide solution in an unhydrated form, with cell dimensions a = 11.849, b = 10.004, c = 9.862 A, beta = 101.30 degrees, monoclinic space group P21 with 4 molecules per cell (2 independent molecules in the asymmetric unit). The structure was determined by direct methods and refined to a discrepancy index R = 0.057. The tri-L-alanine molecules are packed in a parallel pleated sheet arrangement with unusually long amide nitrogen-carbonyl oxygen contacts within sheets. Comparisons are made with the antiparallel pleated sheet structure of tri-L-alanine hemihydrate, previously crystallized from the same solvent system.

Synthesis of (R)-(-)- and (S)-(+)-synadenol (1a and 2a, 95-96% ee) is described. Racemic synadenol (1a + 2a) was deaminated with adenosine deaminase to give (R)-(-)-synadenol (1a) and (S)-(+)-hypoxanthine derivative 5. Acetylation of the latter compound gave acetate 6. Reaction with N, N-dimethylchloromethyleneammonium chloride led to 6-chloropurine derivative 7. Ammonolysis furnished (S)-(+)-synadenol (2a). Absolute configuration of 1a was established by two methods: (i) synthesis from (R)-methylenecyclopropanecarboxylic acid (8) and (ii) X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. Racemic methylenecyclopropanecarboxylic acid (10) was resolved by a modification of the described procedure. The R-enantiomer 8 was converted to ethyl ester 13 which was brominated to give vicinal dibromides 14. Reduction with diisobutylaluminum hydride then furnished alcohol 15 which was acetylated to the corresponding acetate 16. Alkylation-elimination procedure of adenine with 16 yielded acetates 17 and 18. Deprotection with ammonia afforded a mixture of Z- and E-isomers 1a and 19 of the R-configuration. Comparison with products 1a and 2a by chiral HPLC established the R-configuration of (-)-synadenol (1a). These results were confirmed by X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. The latter forms a pseudosymmetric dimer with adenine-adenine base pairing in the lattice with the nucleobase in an anti-like conformation. Enantiomers 1a and 2a exhibit varied enantioselectivity toward different viruses. Both enantiomers are equipotent against human cytomegalovirus (HCMV) and varicella zoster virus (VZV). The S-enantiomer 2a is somewhat more effective than R-enantiomer 1a in herpes simplex virus 1 and 2 (HSV-1 and HSV-2) assays. By contrast, enantioselectivity of antiviral effect is reversed in Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) assays where the R-enantiomer 1a is preferred. In these assays, the S-enantiomer 2a is less effective (EBV) or devoid of activity (HIV-1).

High-resolution structures of the glucosidase inhibitors deoxynojirimycin (dNM) and castanospermine (CAST) have been determined by X-ray diffraction. The crystal parameters are a = 10.751(3) and 8.788(3) A, b = 9.263(3) and 8.172(3) A, c = 7.719(2) and 6.507(2) A, and space group P2(1)2(1)2(1) and P2(1) for dNM and CAST, respectively. (beta = 105.44(8) degrees for CAST.) The absolute configuration of CAST has also been established. Stereochemical comparisons with natural glucosidase substrates such as maltose and methyl glucoside show great similarities in the positioning of functional groups, and indicate the basis for enzyme inhibition. Conformational comparison between dNM and CAST suggests the greater activity of CAST may be due to the fixed axial positioning of the O6 atom; the results have implications for the design of analogues for potential anti-HIV and other antiviral therapies.

No abstract

In the title compound, dimethyl(¿5-[2-(1-methylamino-2-nitroethenylamino)ethylthiometh yl]-2- furyl¿methyl)ammonium chloride, C(13)H(23)N(4)O(3)S(+).Cl(-), protonation occurs at the dimethylamino N atom. The ranitidine molecule adopts an eclipsed conformation. Bond lengths indicate extensive electron delocalization in the N,N'-dimethyl-2-nitro-1, 1-ethenediamine system of the molecule. The nitro and methylamino groups are trans across the side chain C=C double bond, while the ethylamino and nitro groups are cis. The Cl(-) ions link molecules through hydrogen bonds.