A convenient preparation of aldonohydroxamic acids in water and crystal structure of L-erythronohydroxamic acid.

Hydroxamic acids derived from aldonic acids, namely aldonohydroxamic acids, have become an increasingly important class of inhibitors of enzymes involved in the metabolism of carbohydrates. We now report the straightforward preparation of various types of aldonohydroxamic acids by a new methodology involving the use of commercial 50% aqueous hydroxylamine as the source of the free base hydroxylamine that reacts directly with the corresponding aldonolactone dissolved in water. The reaction proceeds almost instantaneously in water at room temperature, yielding generally pure products in quantitative yield. To date, this methodology is probably the most facile and efficient way to synthesize aldonohydroxamic acids. We also determined by X-ray diffraction analysis the first crystal structure of a free aldonohydroxamic acid reported to date. Crystals of L-erythronohydroxamic acid belonged to the monoclinic system, space group P2(1), a=5.511(3), b=7.556(1), c=8.071(3) A, beta=109.10 degrees, and Z=2.

Structure of a hexasaccharide proximal to the hydrophobic region of lipopolysaccharides present in Bordetella pertussis endotoxin preparations.

A branched-chain hexasaccharide containing 3-deoxy-D-manno-oct-2-ulosonic acid was released by detergent-promoted hydrolysis from Bordetella pertussis endotoxin preparations that were first dephosphorylated with aqueous HF and then treated with nitrous acid. Its structure (2) [Formula: See text] was determined by chemical and physical methods. This hexasaccharide is present in all four lipopolysaccharides that make up the B. pertussis strain 1414 (phase 1) endotoxin preparations analysed, and is situated near to the hydrophobic domains. An analogous structure reported previously (ref 7) is erroneous and should be disregarded.

The use of an immobilised cyclic multi-enzyme system to synthesise branched penta- and hexa-saccharides associated with blood-group I epitopes.

The branched hexasaccharide beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)- [beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----6)]-beta-D-Galp-(1----4)-beta -D- GlcOMe (1) was obtained on a 0.1-mmol scale by enzymic bigalactosylation of the tetrasaccharide beta-D-GlcpNAc-(1----3)-[beta-D-GlcpNAc-(1----6)]-beta-D-Galp-(1----4)-b eta- D-GlcOMe by the use of an immobilised multi-enzyme system which regenerated UDP-alpha-D-galactose in situ. The formation of 1 proceeded in two steps. An intermediate compound was identified on the basis of 1H- and 13C-n.m.r. data as the pentasaccharide beta-D-GlcpNAc-(1----3)-[beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----6)]-b eta- D-Galp-(1----4)-beta-D-GlcOMe.

Molecular complexes of nucleosides and nucleotides with a monomeric cationic porphyrin and some of its metal derivatives.

Tetrakis(4-7V-methylpyridyl)porphine (H2TMpyP) and a number of its metal derivatives interact extensively with mononucleotides and mononucleosides in aqueous solution. The complexes formed are of a stacking-type involving extensive overlap of the -systems of the porphyrin and purine or pyrimidine bases. Coulombic attractions help stabilize the complexes but there is no evidence for ligation of the bases to axial sites of the metalloporphyrins. Stability constants determined via NMR and spectrophotometric titrations are larger for purine bases than pyrimidines with a given porphyrin derivative. More dramatic influences on stability result from changing porphyrins. Porphyrins having no axial ligands (e.g., metal-free copper(II), palladium(II), and nickel(II) derivatives) or one axial ligand (Zn(II)) produce much larger interactions with a given nucleotide or nucleoside than do metalloporphyrins having two axial ligands (e.g., Mn(III), Fe(III), or Co(III)). The kinetics of the interaction of H2TMpyP with 2'-deoxyadenosine S'-monophosphate (dAMP) were studied via the laser raman temperature-jump method. The measured rate constants are consistent with a simple stacking model for the interaction.

Soularubinone, a new antileukemic quassionoid from Soulamea tomentosa.

The structure of soularubinone 3, a new antileukemic quassinoid isolated from the leaves of Soulamea tomentosa (Brongn, and Gris), has been established by spectral and chemical methods. It has been shown to be the C-15 beta-hydroxy-isovaleric ester of glaucarubolone. Soularubinone shows significant antineoplastic activity against mouse leukemia P-388 and inhibits cell transformation induced by Rous sarcoma virus. The known quassinoid chaparrinone I has also been isolated.