Serine Methyl Research Articles

Solid-phase synthesis of JBIR-126 (Tambromycin), JBIR-35 and their analogs

The convenience of solid-phase synthesis over solution phase synthesis is well known for peptides for the ease of performing reactions as well as isolation of products. Herein we describe the Fmoc-solid-phase synthesis of natural products JBIR-126 (Tambromycin), JBIR-35 and their analogs. These compounds were prepared by the incorporation of several amino acids at the two possible amidation sites. For the serine terminal region both serine and methyl serine were employed and for the middle segment, flanked by serine region and dihydroisoxazole, different commercially available Fmoc-amino acids and synthesized Fmoc-tambroline were utilized.

Synthesis of block copolymers derived from N-trityl-(S)-serine and pyrene end-labeled poly(methyl methacrylate) or poly(N-isopropylacrylamide) via ATRP

A new monomer bearing N-trityl-l-serine methyl ester in structure, methacryloyloxyethyl carbamoyloxy–N-trityl methyl serine (MTS), was prepared to be further polymerized by atom transfer radical polymerization (ATRP) with pyrene-endcapped poly(methyl methacrylate) (Py–PMMA–Br) or poly(N-isopropylacrylamide) (Py–PNIPA–Br). The resulting block copolymers, poly(methyl methacrylate–block–methacryloyloxyethyl carbamoyloxy–N-trityl methyl serine) (Py–PMMA–b–PMTS) and poly(N-isopropylacrylamide–block–methacryloyloxyethyl carbamoyloxy–N-trityl methyl serine (Py–PNIPA–b–PMTS) were characterized by 1H (13C) NMR, ultraviolet, FTIR and fluorescence spectroscopy, thermal analysis, differential scanning calorimetry (DSC), atomic force microscopy (AFM), scanning electron microscopy (SEM), and gel permeation chromatography (GPC) measurements. The chemical composition in Py–PMMA–b–PMTS was estimated from the 1H NMR analysis that indicated a ratio of the repeating units of 46:19 (MMA:MTS). For the Py–PNIPA–b–PMTS the composition rate in the copolymer was 61:25 (NIPA:MTS). Quenching of the pyrene species with N,N-diethylaniline, nitrobenzene, nitrophenol, potassium iodide, p-nitrotoluene and tetracyanoquinodimethane (TCNQ) in DMF solution excited at 348nm was evidenced, more efficiently being nitrophenol and TCNQ. In this case, the monomer emission at 388–409nm underwent a significant decrease caused of an electron transfer from the electron-reach photoexcited pyrene molecule to the electron-deficient quenchers.

Solution-Phase Parallel Synthesis of Novel Spirooxazolinoisoxazolines

A practical and efficient solution-phase parallel synthesis of spirooxazolinoisoxazolines has been developed. Starting from methyl serine ester, the key steps are (1) acylation with concomitant beta-elimination to form an alpha,beta-unsaturated ester, (2) 1,3-dipolar cycloaddition with an oxime to form an isoxazoline ring, (3) reduction with NaBH(4), and (4) mesylation and in situ cyclization to form an oxazoline ring. All reaction steps and workup procedures were modified to allow the use of automated equipment including a synthesizer, a multifunctional liquid handler, and a vacuum centrifuge. Using this equipment, we synthesized a 100-membered library of spirooxazolinoisoxazoline in high yield, high purity, and excellent regioselectivity.

Studies on Synthesis and Intramolecular Catalyzed Hydrolysis of Thiophosphoramidate Derivatives of Nucleoside

AbstractNovel thiophosphoramidate derivatives of nucleoside analogue as membrane‐soluble prodrugs of the bioactive free nucleotides have been prepared by thiophosphorylation reaction. 2′,3′‐O, O′‐Isopropylidene uridine‐5′‐yl N‐thiophosphoryl serine and threonine methyl esters underwent the intramolecular catalyzed hydrolysis reaction.

Ring-chain tautomerism of oxazolidines derived from serine esters

In spite of an earlier statement (Bull. Chem. Soc. Jpn. *1981, 54, 1844), ring-chain tautomeric mixtures were obtained from serine methyl or ethyl ester with aromatic aldehydes. Tautomeric ratios gave a good correlation according to the equation log K = ϱσ + + log K 0. A clear tendency was also found between the tautomeric ratios and the dielectric constants of the solvents.

AB initio studies of structural features not easily amenable to experiment: Part 64. Conformational analysis and local geometry maps of the model dipeptide N-acetyl N'-methyl serine amide

Using the ab initio gradient procedure with the 4-21G basis set, molecular structures were determined for 17 conformations of the model dipeptide, N-acetyl N'-methyl serine amide (SER), forming a 30° grid in parts of the β, β', C 7 eq, bridge, and α R, regions of its φ, ψ space. The results make it possible to construct local geometry maps which describe the conformationally related changes in the bond distances and angles of the system. Local geometry maps of the backbone parameters N-C(α), C(α)-C', and N-C(α)-C', are found to resemble closely those of the homologous dipeptides of glycine (GLY) and alanine (ALA). In contrast, the conformational energy surface of SER shows characteristic differences compared to GLY and ALA: increasing the complexity of the amino acid side group increases the depth of the surface and, at the same time, makes it possible to construct minimum-energy conformers in different regions which are energetically equivalent. Thus, current GLY, ALA, and SER 4-21G results suggest the following general trend: important, conformationally related structural changes in peptide backbone parameters depend mainly on φ and ψ, whereas, relative φ, ψ energies can change significantly with the nature and the conformational state of the side chain.

Ab initio geometry refinement of some selected structures of the model dipeptide N-acetyl N'-methyl serine amide

Five structures (two each in the C 7 eq - and β-regions, and one in the β′-region of the φ(NC α)ψ (C αC′) potential energy surface) were determined of the model dipeptide N-acetyl N′-methyl serine amide by ab initio gradient geometry refinement at the 4-21G level. Energy differences connected with conformations transitions of the CH 2OH side group in the same region of φψ space are found to be similar to differences connected with transitions between the C 7 eq -and β-regions. Different CH 2OH torsional arrangements can lead to changes of 12° in the backbone parameter, NC αC′, and of approximately 0.005 Å in the NC α bond length. Similar conformationally dependent changes in bond lengths and angles, caused by the side group, are found for the peptide groups. In the most stable conformation investigated in this study, C 7 eq -region, the α-carbon atom is the bridge head of a tricyclic system, consisting of a five-, a six- and a seven-membered ring, each closed by internal hydrogen bonding.

Studies of the Improvement of Antioxidant Effect of Tocopherols. XII

The synergistic antioxidant effects of tocopherol (Toc) and 20 kinds of methyl esters of amino acids on lard and palm oil were investigated by the oven and AOM tests. The amino acid derivatives were used in consideration of the insolubility of their free forms in fats. They were homogeniously dissolved using monoglyceride as the medium, as previously described. The antioxidant effects of them were also studied in the same manner.1) The solubility of the amino acid derivatives was found in most cases to be less than 40ppm.2) On lard, 14 amino acid derivatives had rather antioxidant effects according to the oven test, particularly so in the case of methyl L-tryptophan (L-Trp) and methyl lysine (Lys), but dimethyl L-glutamate (Glu-2) tended to accelate oxidation. However, such effects were not observed by the AOM test. All the derivatives except Glu-2 enhanced the antioxidant effect of Toc according to the oven and AOM tests, and the addition of L-Trp, Lys, methyl proline (Pro) or methyl tyrosine (Tyr) along with the mixture of d-Toc (m-Toc) was particularly effective for this.3) On palm oil, 9 of the amino acid derivatives had rather antioxidant effects by the oven test. Pro and L-Trp did so markedly, but Glu-2 and methyl serine tended to accelate oxidation. With Toc, 12 derivatives showed synergistic effects and the addition of Pro, L-Trp, Try or dimethyl cystine along with m-Toc was particularly effective. Similar effects were observed by the AOM test.

Inhibition in vitro of incorporation of [32P]phosphate into rabbit and human endometrial phospholipids.

Summary. Endometria from rabbits and humans were incubated with [32P]phosphate and several physiological or synthetic amino-alcohols. Sphingomyelin, phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine were then isolated and their specific radioactivities determined. Addition of choline to the media resulted in an increased incorporation of 32P into phosphatidyl choline; neither ethanolamine nor serine had any significant effect on any of the phospholipid classes. Aminomethylpropanol, 3-aminopropanol, triethanolamine, and dimethylaminoisopropanol in concentrations of 0·001 m to 0·1 m resulted in inhibiton of 32P incorporation into all the rabbit endometrial phospholipid classes studied; the first three compounds had a proportionately greater effect upon phosphatidyl choline, whereas dimethylaminoisopropanol had a more uniform inhibitory effect on all the phospholipids. Methyl serine added to the media had no significant effect on incorporation of 32P into any of the phospholipid classes. Incubation of human endometria with 0·01-m concentrations of the above amino-alcohols resulted in similar inhibitory effects on 32P incorporation into the phospholipid classes studied.

A SYNTHESIS OF SERINE AND ITS METHYL ESTER

A SYNTHESIS OF SERINE AND ITS METHYL ESTER