87421-27-0

The total synthesis of dehydromicrosclerodermin B and microsclerodermin J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp-2-CO2H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material.

Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit cystathionine-γ- lyase (CSE). Also described herein are methods for using such CSE inhibitors, alone or in combination with other compounds, for treatin

no abstract published

N-t-Butyloxycarbonyl-amino acids (Boc-) are labile on heating to afford free amino acids, but Boc-aspartic acid gives a kind of polypeptide. This chemical feature of Boc-aspartic acid may be caused by dehydration between two carboxyl groups as well as the formation of a free amino group. Boc-Asparagine may have a similar reactivity to Boc-aspartic acid. This research describes polypeptide formation by heating Boc-asparagine and its isomer Boc-aspartic acid amide.

The present invention relates to compounds capable of inhibiting and/or decreasing the activity of one or more cathepsins, thereby treating and/or preventing various disease states associated with one or more cysteine proteases including, but not limited

A simple route for the synthesis of Boc-protected tetrazole analogs of amino acids starting from Nα-Boc amino acids has been described. The [2 + 3] cycloaddition of Boc-α-amino nitrile and sodium azide in the presence of a catalytic amount of zinc bromide yielded the desired tetrazoles in good yields and purity. All the compounds obtained have been characterized by 1H and 13C-NMR and mass spectral studies. Copyright Taylor & Francis Group, LLC.

The synthesis of a new inhibitor, N-phosphonacetyl-L-isoasparagine (PALI), of Escherichia coli aspartate transcarbamoylase (ATCase) is reported, as well as structural studies of the enzyme·PALI complex. PALI was synthesized in 7 steps from β-benzyl L-aspartate. The KD of PALI was 2 μM. Kinetics and small-angle X-ray scattering experiments showed that PALI can induce the cooperative transition of ATCase from the T to the R state. The X-ray structure of the enzyme·PALI complex showed 22 hydrogen-bonding interactions between the enzyme and PALI. The kinetic characterization and crystal structure of the ATCase·PALI complex also provides detailed information regarding the importance of the α-carboxylate for the binding of the substrate aspartate.

The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thi

The first total synthesis of the thiopeptide antibiotic amythiamicin D is described.

A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the

Enantiospecific syntheses of optically active amino acids containing an oxazole moiety are described. Two different strategies for their insertion in a peptidomimetic chain are also discussed. The procedures presented are based on materials readily available in multigram quantities.

We report here the synthesis and activity of HIV protease inhibitors. In the first stage hydrophobic compounds incorporating a 'carba' bond surrogate or a beta-homologated residue were synthesized. Secondly, we synthesized cyclic compounds in which we incorporated 2-quinoline carboxylic acid in the P3 position and the amino-hydroxyindane moiety in the P'3. The last part of this work was dedicated to a structure/activity study of a peptide substrate. These modifications allowed us to work up the synthesis of new pseudopeptide bonds: amino-amide and hydroxy-amide. Compounds with activity in the micromolar range were actually a starting point for the synthesis of new protease inhibitors.

A series of nonpeptide fibrinogen receptor antagonists based upon the tetrapeptide Arg-Gly-Asp-Arg were prepared. These relatively simple derivatives incorporate a high degree of conformational flexibility that was anticipated to allow them to attain the

The preparation of three new thiazole derivatives from natural products is described, as well as improvements in the synthesis of ethyl 2-aminomethyl-4-thiazolecarboxylate.

Amides formation from protected amino acids and peptides was achieved in an easy and convenient one-pot procedure using di-tert-butyl pyrocarbonate as activating agent in the presence of pyridine and ammonium hydrogencarbonate. The method gave good yields and did not induce racemization during the amidation of urethane protected amino acids.

α-Ketoamide (-NH-CO-CO-) units in intact peptides are generated from Ser/Thr residues via Ru(VIII)-catalyzed C(α)-C side-chain scission. Facets associated with this novel α-carbon modification have been probed with 75 peptides chosen to represent every possible peptide environment. The reactions were carried out at room temperature with in situ generated Ru(VIII) in biphasic (CH3CN/CCl4/pH 3 phosphate buffer, 1:1:2 v/v) medium. Whereas Ser/Thr residues placed at the C-terminal end in peptides undergo N-C bond scission leading to des-Ser/Thr peptide amides - thus acting as Gly equivalents in simulating the α-amidating action of pituitary enzymes - those located at the N-terminal or nonterminal or even at the C-terminal position (protected as amide) were found to undergo oxidative C-C bond scission (involving C(α) and C side-chain bond), resulting in the generation of α-ketoamide (-NH-CO-CO-) units in the intact peptide backbone. The difference in the products arising from C(α)-C side-chain scission of Ser/Thr esters and amides is rationalized on the basis of a common mechanism involving either oxaloesters [PeP-NH-CO-COX; X = OMe] or oxalamides [X = NH2 or NH-Pep] arising from the oxidation of initially formed carbinolamide intermediates [Pep-NH-CH(OH)-COX], wherein, while the former are shown to undergo hydrolysis to terminal amides [Pep-NH2], the oxalamides are found to be stable to hydrolysis. Ancillary noteworthy findings are those of peptide bond scission when contiguous Ser-Ser/Thr-Thr residues are present and the oxidative cleavage at C-terminal Tyr/Trp sites generating des amides. The oxidative methodology presented here is mild, simple, and practical and proceeds with chiral retention. The insensitivity of a large number of amino acid residues, such as Gly, Ala, Leu, Asn, Gln, Asp, Glu, Pro, Arg, Phe, Lys, Val, and Aib, and N-protecting groups, such as Boc, Z, and Bz, toward Ru(VIII) under the experimental conditions should make this methodology practical and useful. Sulfur-containing amino acids Cys and Met get oxidized to sulfones in the products.

Disclosed are tetrahydro-pyrido-indoles having the general formula STR1 which are antagonists towards the neuropeptides cholexystokinin and gastrin processing valuable activities for the treatment of cholecystokinin or gastrin-related disorders of the gas

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Boc- or Z-amino acids were conveniently amidated at room temperature by a one-pot procedure employing ammonium hydrogencarbonate and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in yields of 81-96percent.The benzyl ester-type protector for the side chains of aspartic acid and glutamic acid was not affected by the procedure.