RESUMEN
IspG (also called GcpE) is an oxygen-sensitive [4Fe-4S] enzyme catalyzing the penultimate step of the methylerythritol phosphate (MEP) pathway, a validated target for drug development. It converts 2-C-methyl-d-erythritol-2,4-cyclo-diphosphate (MEcPP) into (E)-4-hydroxy-3-methyl-but-2-enyl-1-diphosphate (HMBPP). The reaction, assimilated to a reductive dehydration, involves redox partners responsible for the formal transfer of two electrons to substrate MEcPP. The 2-vinyl analogue of MEcPP was designed to generate conjugated species during enzyme catalysis, with the aim of providing new reactive centers to be covalently trapped by neighboring amino acid residues. The synthesized substrate analogue displayed irreversible inhibition towards IspG. Furthermore, we have shown that electron transfer occurs prior to inhibition; this might designate conjugated intermediates as probable affinity tags through covalent interaction at the catalytic site. This is the first report of an irreversible inhibitor of the IspG metalloenzyme.
Asunto(s)
Difosfatos , Eritritol , Dominio Catalítico , Transporte de Electrón , Eritritol/metabolismo , PirimidinasRESUMEN
The three-component reaction between a protected α-amino aldehyde, an alcohol and an α-silyloxymalononitrile provides an expedient access to protected α-hydroxy-ß-amino acid derivatives. The prototypical process, performed on N-Cbz-phenylalaninal, is known to proceed with syn diastereoselectivity. The present study demonstrates that the diastereoselectivity of the reaction can be inverted, using the rationale of a Felkin-Anh interaction model. Reactions performed on N,N-dibenzyl-L-phenylalaninal proceed with a high anti diastereoselectivity, providing a panel of synthetically useful ester derivatives of (2S,3S)-allophenylnorstatin. The procedure is exploited to accomplish one of the most efficient syntheses of the title compound to date, in 3 steps (66% yield) from N,N-dibenzyl-L-phenylalaninal.
RESUMEN
In this study, we report the first synthesis of an alkyne-based trehalose monomycolate probe containing a ß-hydroxylated fatty acid and an α-branched chain similar to those of the natural mycolic acid. We demonstrate its utility for the labeling of the mycomembrane of Corynebacteria as well as for the study of mycoloyltransferases.
Asunto(s)
Aciltransferasas/análisis , Membrana Celular/química , Corynebacterium/enzimología , Colorantes Fluorescentes/química , Ácidos Micólicos/química , Aciltransferasas/metabolismo , Membrana Celular/metabolismo , Corynebacterium/citología , Colorantes Fluorescentes/síntesis química , Estructura Molecular , Ácidos Micólicos/síntesis químicaRESUMEN
Using Garner's aldehyde as a substrate, one-pot MAC hydroxyhomologation reactions proceeded in good yields and with anti selectivity for the first time (dr up to 9:1). The products were used to prepare a panel of protected derivatives of erythro-ß-hydroxyaspartic acid and erythro-ß-hydroxyasparagine as single enantiomers in a few steps.
RESUMEN
This paper reports an efficient preparation of bridged bis-ß-CD AZO-CDim 1 bearing azobenzene as a linker and exhibiting high solubility in water. The photoisomerization properties were studied by UV-vis and HPLC and supported by ab initio calculations. The cis/trans ratio of AZO-CDim 1 is 7:93 without irradiation and 37:63 after 120 min of irradiation at 365 nm; the reaction is reversible after irradiation at 254 nm. The photoinduced, switchable binding behavior of AZO-CDim 1 was evaluated by ITC, NMR and molecular modeling in the presence of a ditopic adamantyl guest. The results indicate that AZO-CDim 1 can form two different inclusion complexes with an adamantyl dimer depending on its photoinduced isomers. Both cavities of cis-AZO-CDim 1 are complexed simultaneously by two adamantyl units of the guest forming a 1:1 complex while trans-AZO-CDim 1 seems to lead to the formation of supramolecular polymers with an n:n stoichiometry.
RESUMEN
The asymmetric total synthesis of the originally proposed structure of gymnangiamide, a cytotoxic pentapeptide isolated from the marine hydroid Gymnangium regae Jaderholm, has been achieved. Key to the synthesis was the use of asymmetric hydrogenation of alpha-substituted beta-ketoesters through dynamic kinetic resolution for the preparation of nonproteinogenic chiral amino acids. The disparity of the NMR spectra between the synthetic material containing the L-serine residue and the natural product required a revision of the proposed structure.