Convergent synthesis of a deuterium-labeled serine dipeptide lipid for analysis of biological samples.

Bacterial serine dipeptide lipids are known to promote inflammatory processes and are detected in human tissues associated with periodontal disease or atherosclerosis. Accurate quantification of bacterial serine lipid, specifically lipid 654 [((S)-15-methyl-3-((13-methyltetradecanoyl)oxy)hexadecanoyl)glycyl-l-serine, (3S)-l-serine] isolated from Porphyromonas gingivalis, in biological samples requires the preparation of a stable isotope internal standard for sample supplementation and subsequent mass spectrometric analysis. This report describes the convergent synthesis of a deuterium-substituted serine dipeptide lipid, which is an isotopically labeled homologue that represents a dominant form of serine dipeptide lipid recovered in bacteria.

Expeditious synthesis of Mycobacterium tuberculosis sulfolipids SL-1 and Ac2SGL analogues.

M. tuberculosis sulfoglycolipids SL-1 and Ac2SGL are highly immunogenic and potential vaccine candidates. A short and efficient methodology is reported for the synthesis of SL-1 and Ac2SGL analogues via regioselective functionalization of α,α-D-trehalose employing a highly regioselective late stage sulfation, as a key step. The SL-1 analogues 3a and 4 were obtained in 10 and 9 steps in 13.4% and 23.9% overall yields, respectively. The Ac2SGL analogue 5 was synthesized in 5 steps in 18.4% yield.

Oxo- and thiooxo-imidazo[1,5-c]pyrimidine molecule library: beyond their interest in inhibition of Brucella suis histidinol dehydrogenase, a powerful protection tool in the synthesis of histidine analogues.

Histidinol dehydrogenase (HDH) has been established as a virulence factor for the human pathogen bacterium Brucella suis. Targeting such a virulence factor is a relevant anti-infectious approach as it could decrease the frequency of antibiotic resistance appearance. In this paper, we describe the synthesis of a family of oxo- and thioxo-imidazo[1,5-c]pyrimidines, potential enzyme inhibitors. Beyond their anti-HDH activity, the synthesis approach of these molecules, never described before, is highly original and these oxo- and thioxo- derivatives can improve dramatically the efficiency of the histidine protection pathway for the synthesis of histidine analogues.

Total synthesis of sulfolipid-1.

Sulfolipid-1, a tetra-acylated sulfotrehalose from Mycobacterium tuberculosis, was isolated over 40 years ago. Being a main component of the mycomembrane of M. tuberculosis, its biosynthesis and function have been studied in depth, but the chemical synthesis of sulfolipid-1 has not been reported. The synthesis presented here is based on iterative catalytic asymmetric conjugate additions of methylmagnesium bromide for the preparation of the phthioceranic and hydroxyphthioceranic acid side chains, a double regioselective reductive ring-opening and a fivefold deprotection in the final step.

Synthetic studies toward Mycobacterium tuberculosis sulfolipid-I.

Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. The correlation of its abundance with the virulence of clinical isolates suggests a role for SL-I in pathogenesis, although its biological functions remain unknown. Here we describe the synthesis of a SL-I analogue bearing unnatural lipid substituents. A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. The route developed for the model compound can be readily extended to the synthesis of native SL-I as well as additional analogues for use in the investigation of SL-I's functions.

Ácidos siálicos: distribución, metabolismo y función biológica / Sialic Acids: ocurrence, metabolism and biological function

Los ácidos siálicos están entre las moléculas de mayor importancia del reinoanimal encontrándose también en algunos microorganismos. Son cetoácidos con unesqueleto glucídico de nueve carbonos, están cargados negativamente y se descubrieronen mamíferos aunque se encuentran en la mayor parte de los celomados, enprotostomados (por ejemplo, artrópodos), y deutorostomados (por ejemplo, cordadosy equinodermos). La ruta biosintética del Neu5Ac tiene lugar a través de las siguientesreacciones: a) síntesis de ManAc-6-P, b) síntesis de ManNAc, c) síntesis deNeu5Ac, d) activación del monómero to CMP-Beta-Neu5Ac, y e) transferencia delNeu5Ac a un aceptor. En el catabolismo de estos compuestos las enzimas neuraminidasay N-acetil neuraminato liasa tienen un papel importante. En animales losácidos siálicos están involucrados en interacciones célula-célula e intervienen en laregulación de procesos de reconocimiento celular. En microorganismos están presentesen un número escaso de bacterias y hongos. Estos microorganismos los utilizanpara establecer relaciones simbióticas o parasitarias con animales, para utilizarloscomo fuente de nitrógeno o carbono o para sialilar su propia superficie

Sialic acids are among the most important molecules in the animal kingdomand also occur in some microorganisms. They are alpha-ketoacids with a nine-carbonglycid backbone. They are negatively charged and they were first discovered inmammals, although it appears that they are present in most Coelomata in bothprotostomes (e.g. Arthropoda) and deutorostomes (e.g. Chordata or Echinodermata).The biosynthetic pathway of Neu5Ac proceeds through the following reactions:a) synthesis of ManAc-6-P, b) synthesis of ManNAc, c) synthesis of Neu5Ac, d)activation of the monomer to CMP-Beta-Neu5Ac, and e) transfer of Neu5Ac to theacceptor structure. In the catabolism of this compound, the neuraminidase and Nacetyl-neuraminidate-lyase activities play important roles. In animals, sialic acidsare involved in cell-to-cell interactions and mediate the regulation of recognitionprocess. In microorganisms they are present in a few taxonomically scatteredbacterial and fungal species. These microorganisms establish either symbiotic orparasitic relationships with animals and use host sialic acids either as a carbonnitrogensource or to sialylate their own cell surface