1,721,139 research outputs found
A library approach to the development of chiral supramolecular ligands for asymmetric hydrogenation
No full textThe creation of chiral ligands of simple structure and truly easy preparation is the condition for supramolecular catalysis to become of practical industrial use. To this end, we developed a library of chiral monodentate phosphites, named BenzaPhos,[1] which can be prepared in only two simple steps from readily available compounds. The new ligands, containing a benzoic acid primary amide group capable of hydrogen bonding interactions, showed excellent activity and stereocontrol in the enantioselective hydrogenation of both benchmark substrates and ‘challenging’ olefins.
A series of experiments and computational studies strongly suggest that ligand-substrate H-bonding crucially affects these outstanding catalytic properties.
[1] L. Pignataro, C. Bovio, M. Civera, U. Piarulli, C. Gennari, Chem. Eur. J. 2012, 18, DOI: 10.1002/chem.201201032
Efficient Resolution of Racemic N-Benzyl beta3-Amino Acids by Iterative Liquid-Liquid Extraction with a Chiral (Salen)Cobalt(III) Complex as Enantioselective Selector
No full textThe efficient (up to 93% ee) resolution of racemic N-benzyl beta3-amino acids has been achieved by an iterative (two cycle) liquid-liquid extraction process using a lipophilic chiral (salen)cobalt(III) complex [CoIII(1)(OAc)]. As a result of the resolution by extraction, one enantiomer of the N-benzyl beta3-amino acid predominated in the aqueous phase, while the other enantiomer was driven into the organic phase by complexation to cobalt. The complexed amino acid was then quantitatively released into an aqueous phase, by a reductive (CoIII → CoII) counter-extraction using L-ascorbic acid. The reductive cleavage allowed for the recovery of the Cobalt(II) selector in up to 90% yield (easily re-oxidable to CoIII with air/AcOH)
A carbonylative cross-coupling strategy to the total synthesis of the sarcodictyins : preliminary studies and synthesis of a cyclization precursor
No full textPreliminary studies were conducted on the implementation of a new strategy to the total synthesis OC the common diterpenoid tricyclic skeleton of sarcodictyins and eleutherobin. According to the approach presented, a key retrosynthetic disconnection is devised at the C3-C5 position, identifying a carbonylative cross-coupling reaction as the medium-sized ring forming step. The synthesis of a fully functionalized cyclization precursor, comprising a Z vinylstannane and a carboalkoxy-substituted Z enol triflate as reactive centres is described. (C) 2001 Elsevier Science Ltd. All rights reserved
PEPTIDOMIMETICS CONTAINING NEW BIFUNCTIONAL 2,5-DIKETOPIPERAZINE SCAFFOLDS: SYNTHESIS, CONFORMATIONAL ANALYSIS AND USE AS POTENT INTEGRIN LIGANDS
Full text linkA library of 11 bifunctional 2,5-diketopiperazine (DKP) scaffolds, derived from L- or D-Ser and either L- or D-Asp or D-Glu, was designed and synthesized. All the DKP scaffolds feature a carboxylic acid functionality and an amino group, either protected as Boc or masked as azide, which can be locked in a cis- or trans-relationship as a consequence of the absolute configurations of the two α-amino acids. Moreover, the DKP scaffolds differ from each other for the substitution at the intracyclic nitrogens (N-1, N-4), as they are either mono- or bis-benzylated. The DKP scaffolds, while being derived from α-amino acids, can be seen as constrained dipeptides formed by two β-amino acids or one β- and one γ-amino acid.
Two different synthetic strategies were devised to prepare the mono benzylated scaffolds, depending on the nitrogen substitution (N-1 or N-4). In particular, the synthesis of DKP scaffolds bearing a benzyl group at the serine-derived nitrogen N-4 was accomplished making use of a serine ligation strategy, via the isopeptide.[1] On the other hand, the synthesis of DKP scaffolds bearing a benzyl group at the aspartic acid-derived nitrogen N-1 occurred through the formation of a dipeptide intermediate. Bis N-benzyl substituted scaffolds were easily accessed benzylating mono-substituted advanced intermediates.
An efficient synthesis in solution of eight cyclic peptidomimetics containing a DKP scaffold and the Arg-Gly-Asp (RGD) motif[2] has been developed and optimized. The ligands were tested for their ability to inhibit biotinylated vitronectin binding to integrin αvβ3 and αvβ5 receptors. All the ligands, except for the one containing a cis-scaffold, displayed low nanomolar inhibitory activity for both αVβ3 and αVβ5 integrin receptors, with a slight selectivity in favour of the former receptor. In order to rationalize, on a molecular basis, the affinity of these cyclic RGD peptidomimetics for the αvβ3 receptor, conformational and docking studies were performed by NMR spectroscopy and computational methods.
Two cyclic peptidomimetics containing a DKP scaffold and the isoAsp-Gly-Arg (isoDGR) motif were prepared, combining a solid phase and a solution phase synthetic approach. Very promising results (low nanomolar inhibitory activity) were obtained for their ability to inhibit biotinylated vitronectin binding to the αvβ3 and αvβ5 integrin receptors.
Based on the good results recently obtained by the group of Prof. Oliver Reiser (Univ. Regensburg)[3] in the design of helices, alternating two α- and two β-amino acids, a linear pseudodecapeptide was prepared alternating a cis-DKP, which serves as a ββ-constrained dipeptide, and Ala-Ala as the αα-subunit. The folding properties of the αα,ββ-pseudodecapeptide were studied by NMR spectroscopy, CD spectroscopy and computational methods. The results obtained, though not exhaustive, are indicative of a turn-inducing ability of the cis-DKP.[4]
[1] M. Marchini, M. Mingozzi, R. Colombo, C. Gennari, M. Durini, U. Piarulli, Tetrahedron 2010, 66, 9528-9531.
[2] A. S. M. da Ressurreição, A. Vidu, M. Civera, L. Belvisi, D. Potenza, L. Manzoni, S. Ongeri, C. Gennari, U. Piarulli, Chem. Eur. J. 2009, 15, 12184-12188.
[3] L. Berlicki, L. Pilsl, E. Wéber, I. M. Mándity, C. Cabrele, T. A. Martinek, F. Fülöp, O. Reiser, Angew. Chem. Int. Ed., in press.
[4] a) A. S. M. Ressurreição, A. Bordessa, M. Civera, L. Belvisi, C. Gennari, U. Piarulli, J. Org. Chem. 2008, 73, 652-660; b) R. Delatouche, M. Durini, M. Civera, L. Belvisi, U. Piarulli, Tetrahedron Lett. 2010, 51, 4278-4280
Resolution of racemic N-benzyl-β3-homophenylglycine by iterative liquid-liquid extraction using a chiral cobalt(III) salen complex as enantioselective selector
No full textHighly enantioselective Rh-catalyzed hydrogenations with heterocombinations of pentafluorobenzyl- and methoxybenzyl-derived binaphthyl phosphites
No full textThe Rh-catalyzed hydrogenations of dimethyl itaconate and methyl acetamido acrylate using selected heterocombinations of pentafluorobenzyl- and methoxybenzyl-derived binaphthyl phosphites proved to be highly enantioselective (ee 93–99%). In these selected cases the Rh-heterocomplexes, which were formed in a statistical amount (ca. 50% by 31P NMR), turned out to be more active and selective than the two homocomplexes
A new method for the solution and solid phase synthesis of chiral beta-sulfonopeptides under mild conditions
No full textChiral beta-sulfonopeptides were synthesized both in solution and in the solid phase using the sulfonyl chlorides derived from enantiomerically pure 2-substituted taurines under mild coupling conditions [cat. 4-dimethylaminopyridine (DMAP) and excess methyl trimethylsilyl dimethylketene acetal (MTDA) as a proton trap]. Copyright (C) 1996 Elsevier Science Lt
Chiral (salen)Co(III)(N-benzyl-L-serine) derived phosphites : monodentate P-ligands for enantioselective catalytic applications
No full textReaction of the (S,S)-salen-cobalt(III)-N-benzyl-L-serine complex 2 with four diol-derived chlorophosphites
afforded phosphites 3a–3d in moderate yields (37–72%). Structural studies of these monodentate phosphite ligands and of their Rh-complexes were performed in solution by 1H and 31P NMR spectroscopy.
The ligands were screened in several enantioselective catalytic applications, showing good activity and moderate enantioselectivity in the palladium-catalyzed desymmetrization of meso-cyclopenten-2-ene-1,4-diol biscarbamate
Recent applications of phosphorus reagents: from organic synthesis to stereoselective catalysis
No full textThis chapter will focus on the use of phosphorus (III) compounds in organic synthesis, as reagents, organic catalysts, as well as ligands for transition metal catalysis. The versatility of these compounds stems from the great variety of their steric and electronic properties, which can be conveniently tuned for different applications. For this reason, after a brief presentation of the nomenclature of organic phosphorus compounds, we will discuss the methods for the determination of the steric and electronic paramenters of mainly phosphorus(III) compounds as a means to interpret their reactivity. The reactivity of PIII derivatives will be presented, focussing on a selection of the most recent achievements in the area of organic synthesis and stereoselective organic and transition metal catalysis
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