H+/2e- stoichiometry of the NADH : ubiquinone reductase reaction catalyzed by submitochondrial particles

Nitochondrial NADH:ubiquinone-reductase (Complex I) catalyzes proton translocation into inside-out submitochondrial particles. Here we describe a method for determining the stoichiometric ratio (H) over right arrow (+)/2e(-) (n) for the coupled reaction of NADH oxidation by the quinone accepters. Comparison of the initial rates of NADH oxidation and alkalinization of the surrounding medium after addition of small amounts of NADH to coupled particles in the presence of Q(1) gives the value of n = 4. Thermally induced deactivation of Complex I [1, 2] results in complete inhibition of the NADH oxidase reaction but only partial inhibition of the NADH:Q(1)-reductase reaction. N-Ethylmaleimide (NEM) prevents reactivation and thus completely blocks the thermally deactivated enzyme. The residual NADH:Q(1)-reductase activity of the deactivated, NEM-treated enzyme is shown to be coupled with the transmembraneous proton translocation (n = 4). Thus, thermally induced deactivation of Complex 1 as well as specific inhibitors of the endogenous ubiquinone reduction (rotenone, piericidin A) do not inhibit the proton translocating activity of the enzyme.

Unprecedented regio and stereocontrol in Povarov reaction of benzylidene-(3-nitrophenyl) amine

Typically, Povarov reactions of imines derived from aromatic amines and aromatic aldehydes show poor exo/endo-stereoselectivity and to date no data is available on the regioselectivity of the cyclisation when 3-substituted imines are employed. We have demonstrated that reaction using acyclic enamides as the alkene component with 3-nitro substituted imines is completely regioselective and gave only the 5-nitro substituted tetrahydroquinoline. As a bonus the reaction also became completely exo-selective with the stereochemistry of the E-alkene preserved in the tetrahydroquinoline product.

A stereocontrolled method for the synthesis of D- and L-2-deoxy-C-nucleosides using an intramolecular Sakurai-type cyclisation reaction

A novel synthetic procedure has been developed that provides access to D/L-2-deoxy-C-nucleosides from 3,4-epoxytetrahydrofuran in seven steps and in moderate to good yields. The key chemical transformation was the Lewis acid catalysed intramolecular cyclisation reaction of an acetal for which the stereochemical outcome was dependent of the reagents' ratio.

Reaction of tetracyanoethylene with alpha,beta-unsaturated ketones

Synthesis and Chemistry of simple tetracyanoalkanes is well studied. We performed tetracyanoethylation of unsaturated ketones with an active double bond in alpha-position. The reaction of tetracyanoethylene with alpha,beta-unsaturated ketones may result in four probable products depending on the character of substituents.

Application Of the Michaelis-Arbuzov Reaction to the Synthesis Of Internucleoside 3'-S-Phosphorothiolate Linkages

The 5'-O-monomethoxytrityl-3'-S-(aryldisulfanyl)-3'-deoxythymidines 7 and 8 have been prepared by the reaction of 5'-O-monomethoxytrityl-3'-thiothymidine with the appropriate arenesulfenyl chloride. These disulfides undergo a Michaelis–Arbusov reaction with simple trialkyl phosphites to yield 5'-O-monomethoxytrityl-3'-thiothymidin-3'-yl O,O-dialkyl phosphorothiolates. More interestingly, 3'-deoxy-3'-S-(2, 4-dinitrophenylsulfanyl)-5'-O-monomethoxytritylthymidine 8 reacts with a variety of thymidin-5'-yl dialkyl phosphites to give dithymidine phosphorothiolate triesters with the phosphorothiolate group protected with either a methyl or a 2-cyanoethyl group. 3'-O-(tert-Butyldimethylsilyl)thymidin-5'-yl triethylammoniumphosphonate 17 is converted into the corresponding bis-(O-trimethylsilyl) phosphite by treatment with bis(trimethylsilyl)trifluoroacetamide. in situ Reaction of this phosphate with disulfide 8 gives, after work-up, the dithymidine phosphorothiolate diester directly. Methylation of compound 17 with methyl chloromethanoate, followed by silylation and subsequent reaction with disulfide 8, gives the methyl-protected dithymidine phosphorothiolate triester.