David E. Minter

Alkaloids of the chinese herb guan-bai-fu (aconitum koreanum); guan-fu bases Y and A

Abstract A new alkaloid, guan-fu base Y,has been isolated from Aconitum koreanum (Levl.)Raipaics and shown to be 2-acetoxy-14-hydroxyhetisine ( 2 ) from its nmr (1H, 13C) and mass spectra. A completed assignment of mmr peaka was made with the help of NOE and 2-D experiments which also suggest a revised structure ( 3 ) for guan-fu baae A ( 4 ).

3,4-Didehydropyridine plus cyclopentadiene: [2+2] or [4+2]-cycloaddition ?

Abstract 3, 4-Didehydropyridine ( 2 ) generated from two precursors ( 6 and 7 ) of the diazonium carboxylate 5 reacts with cyclopentadiene to give the [ 4+2 ] -cyclo-addition product 3 rather than the [2+2]-adduct 4 proposed in the literature. The structure of 3 was supported by complete proton and carbon NMR assignments made with the aid of decoupling and 2D experiments.

Synthesis and separation of a diastereomeric pair of phosphonopeptide inhibitors of the cyclic AMP-dependent protein kinase catalytic subunit

Abstract In this paper we report the establishment of a novel procedure to synthesize a nonhydrolyzable phosphonopeptide dead-end inhibitor of the catalytic subunit of cAMP-dependent protein kinase. This procedure has been optimized to maximize the peptide yield and gives a diastereomeric pair of heptapeptides that can be separated on a C-18 reverse phase HPLC column. The two peptides have been characterized by NMR and the ability of these peptides to inhibit the reacton of the catalytic subunit of cAMP-dependent protein kinase. Peptide A has a dissociation constant of 9 micromolar, and is a 10-fold better inhibitor as compared to peptide B. On the basis of this 10-fold greater inhibition afforded by peptide A, this peptide is assiged the all L-form configuration. It is expected that this procedure can easily be adapted to synthesize a variety of different peptide inhibitors which involve a nonhydrolyzable phosphate on an amino acid.

Regiospecipicity in the nucleophilic ring opening reactions of gem-dichlorocyclopropylcarbinyl cations

Abstract gem -Dichlorocyclopropylcarbinyl cations, generated under acidic conditions from the corresponding alcohol or alkene, undergo ring opening by nucleophilic attack exclusively at the halogenated carbon when the alternative electrophilic ring carbon is unsubstituted. In one case, a novel trifluoroacetoxydichloromethyl function has been produced and characterized as a masked carboxylic acid chloride.

Effects of amine-borane structure on the stoichiometry, rate and mechanism of reaction with hypochlorous acid : hydride oxidation versus B-chlorination

Abstract Various ring substituted benzylamine-boranes as well as α-methyl- and N -methylbenzylamine-borane undergo hydride oxidation and N-chlorination on reaction with NaOCl whereas N , N -dimethylbenzylamine-borane is subject to B-chlorination producing a mixture of amine chloroboranes. Results are consistent with previously established patterns of reactivity with alkyl- and non-aromatic heterocyclic secondary amine-boranes being subject to oxidation and their tertiary counterparts to B-chlorination. Current studies reveal the borane adducts of tertiary amines in the quinoline series to react via oxidative pathways. Ring or α-methyl substitution has a negligible effect on the rate of benzylamine-borane oxidation whereas N-methyl substitution causes a three-fold decrease. The benzylamine-borane reaction displays a modest substrate isotope effect ( k BH3 / k BD3 ≅1.3), a pronounced inverse solvent isotope effect ( k D2O / k H 2 O 3) and a pH dependence of rate that indicates saturation kinetics below pH 7.5. It is suggested that both oxidation and B-chlorination involve bimolecular rate-limiting attack of HOCl on amine-borane with different intimate mechanisms arising from correspondingly different activated complexes. A low reactivity of quinoline-monochloroborane with hypochlorite precludes the involvement of a chloroborane as a common intermediate in both processes. The activation free-energy for chlorination of trimethylamine-borane is higher than δ G ≠ values obtained for oxidation of isoquinoline-borane and for a series of benzylamine-boranes. Activation enthalpies are relatively low for both processes. Unlike the chlorination reaction where the entropy term is negligible, δ S ≠ for oxidation accounts for about 20–30% of the activation barrier. It is proposed that details of amine structure determine the mode of attack of amine-borane by HOCl with steric factors playing a dominant role.

Substituent effects on the reductions of quinoline-N-boranes

Abstract Reductions of 2-substituted quinoline- N -boranes by sodium bis-(2-methoxyethoxy)aluminum dihydride lead to 1,2,3,4-tetrahydroquinolines by hydride attack at C-4 and subsequent reduction of the resulting enamine.