Synthesis of the dibenzyl ester of tert-butoxycarbonyl-L-alanyl-D-glutamic acid from racemic glutamic acid

M. V. Frunze Simferopol' State University. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 865–866, November–December, 1991.     

Synthesis and structure of a heterocyclic ansa pyrrole amino acid

We report a synthetic route to ansa pyrrole amino acids via olefin ring-closing metathesis of diene precursors in the presence of Grubbs I catalyst. The dienes were prepared by Grignard addition to pyrrole sulfinyl imines. The success of the macrocyclic ring closure depends on the dienes structure and only in the case of the 13-membered compound 28 sufficient material could be isolated by preparative HPLC separation to investigate its structure spectroscopically. As also rationalized by our computations at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level of theory, 28 is configurationally stable.     

Synthesis and antitumor activity of heterocyclic acid ester derivatives of 20S-camptothecins

A series of heterocyclic acid esters of camptothecins as new compounds had been synthesized by acylation method,their in vitro and in vivo antitumor activities were evaluated.The cytotoxic results showed that 6 possessed the best efficacy on six human cancer cell lines in the six classes of CPTs' derivatives.In vivo testing results indicated that 9 had better antitumor activity against mouse liver carcinoma H_(22) than topotecan.     

Synthesis of isoprenoid acids from isoprenoid ketones by the action of the diethyl ester of carbetboxymethylphosphonic acid

Summary A method for the synthesis of isoprenoid acids is proposed, based on the reaction of isoprenoid ketones with the diethyl ester of carbethoxymethylphosphonic acid.     

Synthesis and cytotoxic activities of a series of novel N-methylbisindolylmaleimide amino acid ester conjugates

A series of novel N-methylbisindolylmaleimides and natural amino acid conjugates were synthesized and evaluated for their inhibitory activity against six tumor cell lines.Most of the compounds exhibited moderate in vitro cytotoxic activities in the range of 10-100μmol/L.     

Synthesis and antitumour activity of arctigenin amino acid ester derivatives against H22 hepatocellular carcinoma

Arctigenin (ARG) is famous in its abundant pharmacological activity. However, many researches in it entered the bottleneck period because of its poor water solubility. The derivatives of ARG have been synthesised with five amino acids which have t-Butyloxy carbonyl (BOC) as a protective group. We examined the effects of removing BOC. The results showed that the amino acid derivatives without protective group have better water solubility and nitrite-clearing ability than ARG. Based on these results, ARG6′ and ARG9′ were selected at a dosage of 40 mg/kg to evaluate their antitumour activity. The percentage inhibition rate of ARG6′ and ARG9′ were 55.87 and 51.40, respectively, which was twice as much as ARG. Furthermore, they could increase liver and kidney indexes and produce less damage in these organs. In brief, this study provides a basis for new drug development.     

Synthesis of the heterocyclic core of martinelline and martinellic acid

A Povarov reaction, between an aromatic imine derived from cinnamaldehyde and a cyclic enamide, was employed to rapidly construct the tricyclic core of the alkaloids martinelline and martinellic acid. The cycloaddition was completely regioselective though the exo/endo selectivity was poor. The diastereoisomers were readily separated by flash chromatography and the relative stereochemistry of the exo-isomer confirmed by single crystal X-ray crystallography. This intermediate was converted to the central core of the aforementioned alkaloids in five additional synthetic operations.     

氨基酸酯-烷基醚混合取代聚膦腈的合成与表征

聚膦腈高聚物,因其良好的生物相容性而用作生物医用材料。若在其侧链引入对热(如烷氧基醚)或对pH值敏感和可生物降解的基团(如氨基酸酯),则可得到具有环境敏感性和可生物降解性能的高聚物,这些高聚物可望作为药物载体,用于药物的控制释放。     

Importance of the single amino acid potential in water for secondary and tertiary structures of proteins

The structure of a protein molecule is considered to be primarily determined by the inter-amino-acid nonbonded interactions, such as hydrogen bonds. However, the conformational space of the polypeptide chain should be simultaneously restricted by the intrinsic conformational preferences of the individual amino acids. We present here precise single amino acid potential (SAAP) surfaces for glycine (For-Gly-NH(2)) and alanine (For-Ala-NH(2)) in water (epsilon = 78.39) and ether (epsilon = 4.335), which were calculated at the HF/6-31+G(d,p) level applying the self-consistent isodensity polarizable continuum model (SCIPCM) reaction field with geometry optimization in the corresponding solvents. The obtained Ramachandran potential surfaces in water showed distinct potential wells in the alpha- and beta-regions. The profiles were in almost perfect agreement with the Ramachandran plots of glycine and alanine residues in folded proteins, suggesting the Boltzmann distributions on the SAAP surfaces. Molecular simulations of polyalanines (For-Ala(n)-NH(2); n = 3-5) by using the SAAP force field equipped with the SCIPCM potentials revealed that the polyalanines readily form 3(10)-helical structures in water but not in vacuo. In ether (hydrophobic environments), the helical structures were relatively stable, but the most stable structure was assigned to a different one. These results indicated that the intrinsic conformational preferences of the individual amino acids (i.e., the SAAPs) in water are of significant importance not only for describing conformations of a polypeptide chain in the random coil state but also for understanding the folding to the secondary and tertiary structures.     

Synthesis and crystal structure of 2,6-bis(N-cytisinomethyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester

By the interaction of the diethyl ester of 2,6-bis(bromomethyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid with two moles of the alkaloid cytosine, the corresponding 2,6-bis(cytisinomethyl) derivative was obtained. The spatial structure of the product was demonstrated by ¹H NMR spectroscopy and X-ray structural analysis.     

Synthesis of d,l-β-carboxyaspartic acid from hydantoin-5-malonic acid diethyl ester

Hydantoin-5-malonic acid diethyl ester was synthesized by reduction of parabanic acid (oxalyl urea) to 5-hydroxy-hydantoin, conversion to 5-chlorohydantoin and condensation with malonic ester. Alkaline hydrolysis gave d,l-β-carboxyaspartic acid.     

Methotrexate analogs. 7. Synthesis of two higher homologs and a positional isomer of methotrexate diethyl ester as potential antitumor agents

Analogs of methotrexate diethyl ester ( 1 ) were prepared, in which the distances separating the ester functions from each other and from the carboxamide function of the p-aminobenzoate moiety were varied via the use of methylene groups as “spacers”. The diethyl esters 3 and 4 , with D,L-α-aminoadipate and D,L-α-aminopimelate side chains in place of L-glutamate, displayed approximately the same order of activity as compound 1 against bacterial and mammalian cells in culture, and were inhibitors of the enzyme dihydrofolate reductase. When given intraperitoneally to L1210 1eukemic mice at a dose of 120 mg./kg. q3d 1,4,7, compound 4 produced a 67% increase in survival and no evidence of toxicity, whereas methotrexate diethyl ester ( 1 ) gave a 44% increase in survival at a dose of 45 mg./kg. q3d 1,4,7 but was toxic at higher doses. The positional isomer 2 was inactive.     

Crystal structure,IR-LD spectroscopic,theoretical and vibrational analysis of valinamide ester amide of squaric acid diethyl ester

Valinamide ester amide of squaric acid has been synthesized and structurally characterized by single crystal X-ray diffraction. Individual molecules are linked into zig-zag helix chains running parallel to [0 1 0] by N–H ? O hydrogen bonds of length 2.7908(19) Å and 2.980(2) Å involving the valinamide nitrogen atoms and the amide carbonyl oxygen atom. An experimental IR spectroscopic characterization and theoretical vibrational analysis have also been performed, using the possibilities of polarized linear-dichroic IR-spectroscopy (IR-LD), based on an orientation technique of the molecules as a suspension in a nematic liquid crystal.     

Synthesis of piperidinones incorporating an amino acid moiety as potential SP antagonists

Substituted (±)-trans-1-benzyl-6-oxo-2-phenylpiperidine-3-carboxamides (type I) and the acylated derivatives of (±)-trans-5-amino-1-benzyl-6-phenylpiperidin-2-one (type II) were prepared by the reaction of (±)-trans-1-benzyl-6-oxo-2-phenylpiperidine-3-carboxylic acid and some common reagents to provide the products in satisfactory yields. Newly synthesized compounds share the same moiety with common SP antagonists and thus similar activities might be expected.