Straightforward synthesis of cyclic and bicyclic peptides

Cyclic peptide architectures can be easily synthesized from cysteine-containing peptides with appending maleimides, free or protected, through an intramolecular Michael-type reaction. After peptide assembly, the peptide can cyclize either during the trifluoroacetic acid treatment, if the maleimide is not protected, or upon deprotection of the maleimide. The combination of free and protected maleimide moieties and two orthogonally protected cysteines gives access to structurally different bicyclic peptides with isolated or fused cycles.

Is the presence of an intrathecal synthesis of immunoglobulins associated with neurocognitive impairment in HIV-infected patients?

Worldwide, the incidence of HIV-associated dementia has decreased However, the prevalence of HIV-associated neurocognitive disorders (HAND), mostly the milder forms, i.e. mild neurocognitve disorders (MND) and asymptomatic neurocognitive impairments (ANI) has increased in the combined antiretroviral therapy (cART) era. Indeed, 20% to 60% of well- treated HIV-infected patients, i.e. with undetectable HIV viremia, still present HAND in the cART era. HAND are characterized by psychomotor slowing, memory loss, and attention deficit. Possible explanations for this paradoxical phenomenon encompass: increased survival of HIV- infected patients thank to cART, low grade inflammation of the brain insufficient penetrance of antiretroviral drugs through the blood brain barrier (BBB), or on the contrary, toxic effect of some antiretroviral drugs. These somewhat contradictory hypotheses underline our poor understanding of HAND physiopathology. Here, we aim at determining whether the intrathecal synthesis of immunoglobulins G (IgG), hereafter referred as cerebrospinal fluid oligoclonal band (CSF OB), may help us in better understanding the immunopathogenesis of cognitive disorders. By analogy with other infection, such as syphilis or neuroborreliosis (9, 10), one can assume that, in the case of HIV-infected patients, the CSF OB are directed against HIV proteins (11). Nevertheless, in the case of HIV, the meaning of such CSF OB is unclear. Indeed, it is unknown whether this intrathecal inflammatory reaction is beneficial (viral control) or harmful (brain parenchyma destruction by the different inflammatory factors). Here, we looked at the association between CSF OB and cognitive disorders in HIV-infected patients, hypothesizing that if these CSF OB are protective, one should see an inverse correlation with the presence of cognitive disorders.

Vulnerability of stream biota to climate change in mediterranean climate regions: a synthesis of ecological responses and conservation challenges

Freshwater species worldwide are experiencing dramatic declines partly attributable to ongoing climate change. It is expected that the future effects of climate change could be particularly severe in mediterranean climate (med-) regions, which host many endemic species already under great stress from the high level of human development. In this article, we review the climate and climate-induced changes in streams of med-regions and the responses of stream biota, focusing on both observed and anticipated ecological responses. We also discuss current knowledge gaps and conservation challenges. Expected climate alterations have already been observed in the last decades, and include: increased annual average air temperatures; decreased annual average precipitation; hydrologic alterations; and an increase in frequency, intensity and duration of extreme events, such as floods, droughts and fires. Recent observations, which are concordant with forecasts built, show stream biota of med-regions when facing climate changes tend to be displaced towards higher elevations and upper latitudes, communities tend to change their composition and homogenize, while some life-history traits seem to provide biota with resilience and resistance to adapt to the new conditions (as being short-lived, small, and resistant to low streamflow and desiccation). Nevertheless, such responses may be insufficient to cope with current and future environmental changes. Accurate forecasts of biotic changes and possible adaptations are difficult to obtain in med-regions mainly because of the difficulty of distinguishing disturbances due to natural variability from the effects of climate change, particularly regarding hydrology. Long-term studies are needed to disentangle such variability and improve knowledge regarding the ecological responses and the detection of early warning signals to climate change. Investments should focus on taxa beyond fish and macroinvertebrates, and in covering the less studied regions of Chile and South Africa. Scientists, policy makers and water managers must be involved in the climate change dialogue because the freshwater conservation concerns are huge.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.

Synthesis of angiotensin-converting enzyme (ACE) inhibitors: an important class of antihypertensive drugs

This report outlines the discovery, the design and development of new compounds, and, structure-activity relationships for this drug category. Updated approaches to planned syntheses of new worthy ACE-inhibitors are also exploited.

Synthesis of 2-(alkylamino)-1-phenylethane-1-thiosulfuric acids, potential schistosomicides

The total synthesis of seven here-to-fore unreported aromatic aminoalkanethiosulfuric acids, their physical properties and those of the aminoalcohol and bromoalkanamine intermediates are reported. All structures were established by including ¹H and 13C NMR, IR and MS spectroscopy and elemental analysis.

Enantioselective synthesis of aziridines using asymmetric transfer hydrogenation as a precursor for chiral derivatives used as bonding agent for rocket solid propellants

A rapid, expedient and enantioselective method for the synthesis of beta-hydroxy amines and monosubstituted aziridines in up to 99% e.e., via asymmetric transfer hydrogenation of a-amino ketones and cyclisation through treatment with tosyl chloride and base, is described. (1R,2R)-N-(para-toluenesulfonyl)-1,2-ethylenediamine with formic acid has been utilised as a ligand for the Ruthenium (II) catalysed enantioselective transfer hydrogenation of the ketones.The chiral 2-methyl aziridine, which is a potentially more efficient bonding agent for Rocket Solid Propellant has been successfully achieved.

The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indole

N-3-(1-Methylindol-3-yl)propan-N-(2,2,2-trichloroethoxysulfonyl)guanidine was synthesized from 3-formyl-1-methylindole in six steps and subjected to conditions intended to convert the side-chain into a 2-iminotetrahydropyrimidine- containing product, of relevance to a possible synthesis of the aplicyanins. An alternative reaction course was observed, resulting in the formation of a new tetracyclic system.

Total synthesis of lamellarin D and analogs library

Larnellarins are a group of marine natural products isolated from the prosobranch mollusc Lamellaria sp., the ascidian Didemnum sp., and the sponge Dendrilla Cactos. Several of them exhibit interesting biological activities. Natural as well as synthetic lamellarins should be excellent candidates for the development of new drugs due to their unique skeletal structure and their important biological activities especially as antitumor agents. Lamelarin O has been recently characterized as a topoisomerase 1-targeted anti tumor agent. A variety of synthetic approaches have been developed for this family of alkaloids. Herein we describe a new route to the synthesis of Lamellarin D, from a methyl 2-pyrrolecarboxylate. Transformation of the starting material into the scaffold, a substituted 5,6-dihydropyrrolo (2,l ­a)isoquinoline (5,6-DHPl), was afforded by N-alkylation followed by intramolecular Heck cyclization. From this scaffold the synthetic strategy is based on two sequential regioselective bromination!Suzuki cross-coupling reactions which permitted the introduction of differently substituted aryl groups on positions 1 and 2 followed by oxidation, deprotection, and lactonization.

The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indole

N-3-(1-Methylindol-3-yl)propan-N-(2,2,2-trichloroethoxysulfonyl)guanidine was synthesized from 3-formyl-1-methylindole in six steps and subjected to conditions intended to convert the side-chain into a 2-iminotetrahydropyrimidine- containing product, of relevance to a possible synthesis of the aplicyanins. An alternative reaction course was observed, resulting in the formation of a new tetracyclic system.

Review of the synthesis of layered double hydroxides: a thermodynamic approach

The synthesis of layered double hydroxides (LDHs) by hydrothermal-LDH reconstruction and coprecipitation methods is reviewed using a thermodynamic approach. A mixture model was used for the estimation of the thermodynamics of formation of LDHs. The synthesis and solubility of LDHs are discussed in terms of standard molar Gibbs free energy change of reaction. Data for numerous divalent and trivalent metals as well as for some monovalent and tetravalent metals that may be part of the LDH structure have been compiled. Good agreement is found between theoretical and experimental data. Diagrams and tables for the prediction of possible new LDH materials are provided.

On the application of knoevenagel condensation for the synthesis of benzylidene benzothiazine compounds and structural study

The synthesis and physico-chemical properties of new 6-acetylamino or 6-benzoyl-amino 2-benzylidene-4-methyl-4H-benzo[1,4]thiazin-3-ones and 6-benzoylamino or 6-nitro 2-benzylidene-4H-benzo[1,4]thiazin-3-ones are described. These benzylidene benzothiazine compounds were prepared by the Knoevenagel condensation with benzaldehydes. The configurations and conformations of benzylidene benzothiazine derivatives were optimised using the semi-empirical method AM1.