Marc Revés

Primary and Secondary Aminophosphines as Novel P-Stereogenic Building Blocks for Ligand Synthesis†

Chiral phosphine ligands are central to asymmetric metal catalysis. The effect of the majority of these ligands arises from the chirality of their backbones; however, P-stereogenic (P*) ligands have garnered renewed interest. After the decisive work of Knowles and co-workers with PAMP and DIPAMP ligands, several efficient syntheses of all-carbon P* compounds have been reported. In contrast, P* compounds that contain heteroatoms directly linked to the phosphorus center are scarce, and have found little application in catalysis. This class of substances includes secondary phosphine oxides, which exist in equilibrium with their trivalent phosphinite form. P* aminophosphines, which are the corresponding nitrogen analogues, are even more rare, as free primary aminophosphines tend to dimerize with the evolution of ammonia. However, Kolodiazhnyi et al. have reported that borane aminophosphines of type I are stable and that they can be obtained in diastereomerically pure form using 2-phenylethylamine as a chiral amine (Scheme 1). Nonetheless, type I compounds do not have any reported applications in asymmetric catalysis, nor has their hydrogenolysis been described. We envisioned that reductive cleavage of the arylethyl fragment should provide boraneprotected primary aminophosphines of type II, which would be amenable to further transformations and become useful P* building blocks in catalysis. Herein, we report the synthesis of enantiopure P-chiral primary and secondary aminophosphines (II) and diphosphinoamines (III). We began by investigating the hydrogenolysis of the known compound 1a, which contains a tert-butyl(phenyl)phosphinamine moiety (Scheme 2), under various

N-Phosphino-p-tolylsulfinamide Ligands: Synthesis, Stability, and Application to the Intermolecular Pauson−Khand Reaction

Here we synthesized a family of racemic and optically pure N-phosphino-p-tolylsulfinamide (PNSO) ligands. Their stability and coordination behavior toward dicobalt-alkyne complexes was evaluated. Selectivities of up to 3:1 were achieved in the ligand exchange process with (mu-TMSC2H)Co2(CO)6. The resulting optically pure major complexes were tested in the asymmetric intermolecular Pauson-Khand reaction and yielded up to 94% ee. X-ray studies of the major complex 18a indicated that the presence of an aryl group on the sulfinamide reduces the hemilabile character of the PNSO ligands.

Tetramethylnorbornadiene, a versatile alkene for cyclopentenone synthesis through intermolecular Pauson-Khand reactions.

1,2,3,4-Tetramethyl-bicyclo[2.2.1]hepta-2,5-diene (TMNBD, for tetramethylnorbornadiene) has been prepared and used successfully as an acetylene equivalent in the synthesis of substituted cyclopentenones. TMNBD is easily accessible on a multigram scale and displays excellent reactivity toward the intermolecular Pauson-Khand reaction. Conjugate additions on the resulting tricyclic compounds proceed with exquisite diastereoselectivity. The retro-Diels-Alder reaction of these TMNBD derivatives occurs under much smoother conditions than those required for its norbornadiene homologues.

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations.

Summary The interaction of imines with isocyanides has been studied. The main product results from a sequential process involving the attack of two units of isocyanide, under Lewis acid catalysis, upon the carbon–nitrogen double bond of the imine to form the 4-membered ring system. The scope of the reaction regarding the imine and isocyanide ranges has been determined, and also some mechanistic variations and structural features have been described.

Tetrasubstituted Imidazolium Salts as Potent Antiparasitic Agents against African and American Trypanosomiases

Imidazolium salts are privileged compounds in organic chemistry, and have valuable biological properties. Recent studies show that symmetric imidazolium salts with bulky moieties can display antiparasitic activity against T. cruzi. After developing a facile methodology for the synthesis of tetrasubstituted imidazolium salts from propargylamines and isocyanides, we screened a small library of these adducts against the causative agents of African and American trypanosomiases. These compounds display nanomolar activity against T. brucei and low (or sub) micromolar activity against T. cruzi, with excellent selectivity indexes and favorable molecular properties, thereby emerging as promising hits for the treatment of Chagas disease and sleeping sickness.

Identification and Characterization of Sterol Acyltransferases Responsible for Steryl Ester Biosynthesis in Tomato

Steryl esters (SEs) serve as a storage pool of sterols that helps to maintain proper levels of free sterols (FSs) in cell membranes throughout plant growth and development, and participates in the recycling of FSs and fatty acids released from cell membranes in aging tissues. SEs are synthesized by sterol acyltransferases, a family of enzymes that catalyze the transfer of fatty acil groups to the hydroxyl group at C-3 position of the sterol backbone. Sterol acyltransferases are categorized into acyl-CoA:sterol acyltransferases (ASAT) and phospholipid:sterol acyltransferases (PSAT) depending on whether the fatty acyl donor substrate is a long-chain acyl-CoA or a phospolipid. Until now, only Arabidopsis ASAT and PSAT enzymes (AtASAT1 and AtPSAT1) have been cloned and characterized in plants. Here we report the identification, cloning, and functional characterization of the tomato (Solanum lycopersicum cv. Micro-Tom) orthologs. SlPSAT1 and SlASAT1 were able to restore SE to wild type levels in the Arabidopsis psat1-2 and asat1-1 knock-out mutants, respectively. Expression of SlPSAT1 in the psat1-2 background also prevented the toxicity caused by an external supply of mevalonate and the early senescence phenotype observed in detached leaves of this mutant, whereas expression of SlASAT1 in the asat1-1 mutant revealed a clear substrate preference of the tomato enzyme for the sterol precursors cycloartenol and 24-methylene cycloartanol. Subcellular localization studies using fluorescently tagged SlPSAT1 and SlASAT1 proteins revealed that SlPSAT1 localize in cytoplasmic lipid droplets (LDs) while, in contrast to the endoplasmic reticulum (ER) localization of AtASAT1, SlASAT1 resides in the plasma membrane (PM). The possibility that PM-localized SlASAT1 may act catalytically in trans on their sterol substrates, which are presumably embedded in the ER membrane, is discussed. The widespread expression of SlPSAT1 and SlASAT1 genes in different tomato organs together with their moderate transcriptional response to several stresses suggests a dual role of SlPSAT1 and SlASAT1 in tomato plant and fruit development and the adaptive responses to stress. Overall, this study contributes to enlarge the current knowledge on plant sterol acyltransferases and set the basis for further studies aimed at understanding the role of SE metabolism in tomato plant growth and development.