0000000000172757
AUTHOR
Elzbieta Masiukiewicz
Acetylation of 5-Amino-1H-[1,2,4]triazole Revisited
The products of the acetylation reactions of the common herbicide 5-amino-1H-[1,2,4]triazole were investigated using HPLC, GC-MS, 1H NMR, and FTIR spectroscopy. The conventional annular monoacetylation procedures with acetyl chloride are not regioselective and furnish a mixture of isomers. Traditional diacetylation in neat acetic anhydride under reflux produces a mixture of di-, mono-, and triacetylated derivatives. By using equivalent amounts of acetic anhydride in a dimethylformamide solution, a rapid and selective annular monoacetylation of 5-amino-1H-[1,2,4]triazole was achieved. The monoacetylation proceeds via the formation of the intermediate, 1-acetyl-3-amino-1H-[1,2,4]triazole, whi…
A ONE-POT SYNTHESIS OFNαBENZYLOXYCARBONYLNω-t-BUTOXYCARBONYL-L-ORNITHINE AND L-LYSINE
Convenient High Yielding Gram Scale Solution Synthesis of Methionine-Enkephalin.
A simple, large-scale synthesis of a cytokine, methionine-enkephalin, Tyr-Gly-Gly-Phe-Met, has been elaborated. Classical solution peptide chemistry methods without protection of amino acid side-chain functions and 1+(2+2) segment condensation were used. A nine-step synthesis from commercial amino acid derivatives was developed with yields ranging from 86% to 99%, averaging 92%. The purity of all intermediates was found to be 99.0-100% by HPLC. The process has been used to prepare greater than 150 g quantities of the pentapeptide as a monohydrate of 100% purity. Hydantoin formation was observed during saponification of Boc-Tyr-Gly-Gly-Phe-Met-OMe and minimised.
Large Scale Synthesis of Mono- and Di-urethane Derivatives of Lysine.
Orthogonally protected diurethane derivatives of lysine are valuable materials for peptide syntheses. An example is ZLys(Boc), which is exploited in the industrial production of certain well-established peptide drugs. 3,4) Another derivative is Fmoc-Lys(Boc), which is in common use in the laboratory synthesis of peptides. 5) The simplest route to these lysine derivatives seems to be using the copper complex for simultaneous protection of the a-amino and a-carboxyl function, N e -tert-butoxycarbonylation and then copper detachment. The obtained Lys(Boc) might be then subjected to N a -benzyloxycarbonylation.
Increased LH and FSH release from the anterior pituitary of ovariectomized rat, in vivo, by copper-, nickel-, and zinc-LHRH complexes.
Abstract The effect of Cu 2+ , Ni 2+ , Zn 2+ and their complexes with LHRH on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) was estimated in in vivo experiments with the use of the method proposed by Ramirez and McCann. Ovariectomized, estradiol, and progesterone pretreated rats were injected intraveneously either with LHRH alone, a metal ion alone, a mixture of metal and hormone, or a metal-LHRH complex. A metal alone or a mixture of it with LHRH did not affect gonadotropin release at all or no more than LHRH alone. However, the complex of Cu 2+ with LHRH brought about a high release of LH and even higher release of FSH. This indicates that copper complex i…
AN IMPROVED SYNTHESIS OFNα-BENZYLOXYCARBONYL-L-LYSINE
Improved scalable syntheses of mono- and bis-urethane derivatives of ornithine.
In the search for a practical route to ornithine bisurethane derivatives useful for peptide synthesis, we elaborated the simple and efficient (86% yield) synthesis of N(epsilon)-tert-butoxycarbonyl-L-ornithine copper(II) complex (1). This served as substrate for obtaining N(epsilon)-tert-butoxycarbonyl-L-ornithine (2), N(alpha)-benzyloxycarbonyl-N(epsilon)-tert-butoxycarbonyl-L-ornithine (3) and N(alpha)-(9-fluorenyl)methoxycarbonyl-N(epsilon)-tert-butoxycarbonyl-L-ornithine (4). These were synthesized in 94-95% yields and with a purity above 99%.
Synthesis, structure and properties of N-acetylated derivatives of methyl 5-amino-1H-[1,2,4]triazole-3-carboxylate.
Methyl 5-amino-1H-[1,2,4]triazole-3-carboxylate hydrochloride (1). and free ester (2). were obtained and 2 was reacted with Ac(2)O to give the acetylated products 3-6. Compounds 1-6 were studied using HPLC, GC-MS, FTIR and multinuclear NMR spectroscopy, including the cross-polarisation magic angle spinning (CPMAS) technique. The results of the acetylation of 2 were compared to those of the acetylation of 5-amino-1H-[1,2,4]triazole, and for 2 a significant decrease in the susceptibility to acetylation was found. The reaction of 2 with Ac(2)O at 20 degrees C, regardless of the amount and the concentration of the latter, including neat Ac(2)O, proceeds fully regioselectively and leads to one p…
ARGININE, HISTIDINE AND TRYPTOPHAN IN PEPTIDE SYNTHESIS. THE INDOLE FUNCTION OF TRYPTOPHAN
Molecular and crystal structure of Nα-(9-fluorenyl)-methoxycarbonyl-L-ornithine hydrochloride diethyl ether solvate
The solid-state conformation of the first N-protected ornithine derivative has been established by X-ray analysis. The hydrochloride of Nα-(9-fluorenyl)methoxycarbonyl-l-ornithine crystallises as diethyl ether solvate. The backbone (ω0 ϕ, ψ χ1) torsion angles are (174.9°,–84.0°, 145.9°,–171.0°). The conformation of the urethane amide bonds istrans. The ornithine aliphatic side chain adopts preferred fully extended conformation which is stabilised by the hydrogen bonding of the-NH3+ group to the diethyl ether molecule, carboxyl group and Cl− anions.
The synthesis, structure and properties of N-acetylated derivatives of ethyl 3-amino-1H-pyrazole-4-carboxylate.
Ethyl 3-amino-1H-pyrazole-4-carboxylate (1) was yielded through total synthesis and reacted with acetic anhydride to give the acetylated products 2-6. Compounds 1-6 were studied with HPLC, X-ray, FT-IR, (1)H-NMR, (13)C-NMR and MS. Acetylation was carried out in solvents of various polarity, namely; chloroform; dioxane; DMF; acetic anhydride, at room temperature and at boiling points; and in the presence and absence of DMAP. The acetylated products are mainly nitrogen atoms in the ring. The position of the ring proton in the solution was based on NOESY; multinuclear HMBC, HSQC spectra and calculations. For equivalent amounts (1-1.5 mol) of acetic anhydride at room temperature two products of…
ChemInform Abstract: Arginine, Histidine, and Tryptophan in Peptide Synthesis. The Indole Function of Tryptophan
The Molecular and Crystal Structure of tert-Butyl N.ALPHA.-tert-Butoxycarbonyl-L-(S-trityl)cysteinate and the Conformation-Stabilizing Function of Weak Intermolecular Bonding.
The title compound, C31H37NO4S [systematic name: (R)-tert-butyl-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propanoate] is an L-cysteine derivative with three functions: NH2, COOH and SH, blocked by protecting groups tert-butoxycarbonyl, tert-butyl and trityl, respectively. The main chain of the molecule adopts the extended, nearly all-trans C5 conformation with the intramolecular N-H...O=C hydrogen bond. The urethane group is not involved in any intermolecular hydrogen bonding. Only weak intermolecular hydrogen bonds and hydrophobic contacts are observed in the crystal structure. These are C-H...O hydrogen bonds and CH/pi interactions with donor...acceptor distances, C...O ca. 3.5 A a…
Susceptibility of Methyl 3-Amino-1H-pyrazole-5-carboxylate to Acylation
Abstract In the search for a new method of synthesis of hybrid peptides with aminopyrazole carboxylic acid, we tried to force selective acylation at the aromatic amino group instead of at the ring nitrogen atom with fairly gentle acylating agents. The acylating agents used were acid anhydrides: acetic anhydride, tert-butyl pyrocarbonate, and 2-(2-methoxyethoxy)ethoxyacetic acid/dicyclohexylcarbodiimide. We succceded in acylation at this amino group with almost none at the ring nitrogen atom. Sometimes, however, acylation in small quantities at the ring nitrogen atom was observed as a by-product. To remove this by-product, imidazole was used. Thus, we were able to obtain the hybrid peptides …
SCALABLE SYNTHESES OFNα-BENZYLOXYCARBONYL-l-ORNITHINE AND OFNα-(9-FLUORENYLMETHOXY)CARBONYL-l-ORNITHINEE
(2002). SCALABLE SYNTHESES OF N α-BENZYLOXYCARBONYL-l-ORNITHINE AND OF N α-(9-FLUORENYLMETHOXY)CARBONYL-l-ORNITHINEE. Organic Preparations and Procedures International: Vol. 34, No. 5, pp. 531-537.
Large-Scale Synthesis of Mammalian Gonadoliberin without protection of side-chain functions
A simple, Large-scale preparation of mammalian gonadoliberin was elaborated using classical solution methods without protecting side-chain functions. At the final stage, a hexapeptide segment was condensed with the corresponding tetrapeptide and the obtained decapeptide was purified by a single chromatographic procedure on silica gel. The total efficiency of the whole synthesis and the purity of the product amounted to 34% and 98.3%, respectively.
Binding of Cu2+, Zn2+, and Ni(2+)-GnRH complexes with the rat pituitary receptor.
Complex of copper with the gonadotropin-releasing hormone, GnRH, competed more efficiently for the GnRH receptor than native GVRH, while complexes of nickel with GnRH and zinc with GnRH had slightly lower affinity. Copper ion added to the incubation mixture inhibited the buserelin binding to the receptor.
Synthesis of Mammalian Gonadoliberin Analogs with the N-terminal glutamine or glutamine or glutamic acid
Synthesis of two mammalian gonadoliberin analogs, [Gln1]GnRH and [Glu1]GnRH, in solution by the peptide segment coupling of the [(2 + 4) + 4] type has been described.
ChemInform Abstract: Convenient High Yielding Gram Scale Solution Synthesis of Methionine-Enkephalin.
A simple, large-scale synthesis of a cytokine, methionine-enkephalin, Tyr-Gly-Gly-Phe-Met, has been elaborated. Classical solution peptide chemistry methods without protection of amino acid side-chain functions and 1+(2+2) segment condensation were used. A nine-step synthesis from commercial amino acid derivatives was developed with yields ranging from 86% to 99%, averaging 92%. The purity of all intermediates was found to be 99.0-100% by HPLC. The process has been used to prepare greater than 150 g quantities of the pentapeptide as a monohydrate of 100% purity. Hydantoin formation was observed during saponification of Boc-Tyr-Gly-Gly-Phe-Met-OMe and minimised.
Peptide synthesis with 5-amino-1-methyl-1H-[1,2,4]triazole-3-carboxylic acid
Abstract In the search for the peptide synthesis of new potential lexitropsins, starting with methyl 5‐amino‐1‐methyl‐1H‐[1,2,4]triazole‐3‐carboxylate 1a, we synthesized the chloroacetyl derivative of 2a, which was hydrolyzed to acid 2b and ammonolyzed to the peptide 2c. A more effective route was the use of (t‐butoxycarbonyl)glycyl‐benzotriazolide 3 to the acylation 1a, which leads the N/C protected peptide 4. This peptide was selectively N‐deprotected to be the useful segment 5 for further peptide syntheses to the N‐terminus. It was also C‐deprotected, that is hydrolyzed to give peptide 2c for further C‐extension. To the best of our knowledge, this is the first peptide that is a derivativ…
Ovulation-inducing activity of luliberin (LHRH) complexed by copper(II), nickel(II), and zinc(II) ions.
We have shown that the complexation of luteinizing hormone releasing hormone, luliberin (LHRH), a hypothalamic neurohormone, by Cu(II), Ni(II), and Zn(II) may affect its basic, ovulation-inducing potency in the dose responsive manner. Some explanation of the obtained results are offered here.