10.1021/jm8015798
The research focuses on the structure-activity study of new inhibitors for human betaine-homocysteine S-methyltransferase (BHMT), an enzyme that catalyzes the transfer of a methyl group from betaine to L-homocysteine, producing dimethylglycine and L-methionine. The purpose of the study was to design and synthesize a series of BHMT inhibitors that mimic the hypothetical transition state of BHMT substrates, with the aim of developing potent and selective inhibitors to better understand the enzyme's role in sulfur metabolism, osmolytic balance, and other physiological functions. The researchers synthesized and tested various compounds, including analogues with NH, N(CH3), or N(CH3)2 groups separated by different spacers from the homocysteine sulfur atom. They found that only certain inhibitors, particularly those without a nitrogen atom in the S-linked alkyl chain, such as (RS,RS)-5-(3-amino-3-carboxypropylthio)-3-methylpentanoic acid and (RS)5-(3-amino-3-carboxypropylthio)-3,3-dimethylpentanoic acid, showed high potency in inhibiting BHMT. The study concluded that BHMT does not tolerate certain betaine mimics, especially the presence of a nitrogen atom, in these inhibitors, which was surprising and suggests potential conformational changes of BHMT upon binding of substrates/products and inhibitors. The chemicals used in the process included various organic compounds, such as gamma-aminobutyrolactone, 3-mercaptopropionic acid, diethyl acetamidomalonate, and a range of other alkylating agents and protected amino acids, as well as reagents for synthesis and deprotection steps.
10.1055/s-0028-1087940
This research details a novel Azide-Free Synthesis of Oseltamivir, an anti-influenza drug, from L-Methionine. The purpose of the study was to develop an alternative synthesis method that avoids the use of hazardous azide reagents, addressing the safety and availability concerns associated with the commercial production of Oseltamivir, which relies heavily on semisynthesis from less available shikimic acid. The researchers successfully developed a new synthetic pathway that utilizes the Staudinger reaction for the highly enantioselective and stereoselective construction of the three contiguous chiral centers of Oseltamivir. The conclusions highlight the method's advantages of using readily available starting materials, an azide-free synthetic route, and the highly stereoselective construction of the target molecule's chiral centers.
10.1016/j.bmcl.2009.07.065
The research focuses on the design, synthesis, and biological evaluation of new Ras CAAX mimetics. These compounds were designed by replacing cysteine in the Ras protein's C-terminal CAAX tetrapeptide with 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, and using pluri-substituted biphenyl systems as internal spacers and AA dipeptide bioisosteres. The resultant compounds were linked to the methyl ester of L-methionine, glycine, or L-leucine by an amide bond. The synthesized compounds were tested for their antiproliferative effects on human aortic smooth muscle cells (SMCs) and their ability to inhibit Ras prenylation. The most potent compound was found to be the methionine derivative with a methyleneoxy linker between benzodioxane and 2-methylbiphenyl, which demonstrated significant antiproliferative activity and direct interference with Ras prenylation. The study highlights the importance of the linker between the dioxane and biphenyl core and the o-substitution on the biphenyl core for the observed biological activities.
10.1080/00397910903051259
The research explores the synthesis of N-phenyl methyl esters of various amino acids using diphenyliodonium bromide as a key reagent. The study focuses on the efficient and selective N-phenylation of α-amino acids, including glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid. The process involves converting the amino acids into their methyl ester hydrochloride salts, followed by neutralization to obtain free amines. These amines are then subjected to N-phenylation in the presence of diphenyliodonium bromide, silver nitrate, and a catalytic amount of copper bromide. The chiral integrity of the amino acids is maintained throughout the reactions, as confirmed by the synthesis of dipeptides for each N-phenyl amino acid. The structures of the new compounds are characterized using IR, 1H, and 13C NMR spectroscopy, as well as CHN microanalysis or high-resolution mass spectrometry. The study highlights the utility of diphenyliodonium bromide in the synthesis of N-phenylated amino acids, demonstrating good to excellent yields and maintaining the chirality of the starting amino acids.
10.1002/hlca.19500330323
This study focuses on the synthesis and analysis of various derivatives of p-aminosalicylic acid. The key chemicals involved include 2-nitro-p-toluidine, ethyl chloroformate, and sodium methoxide, which are used to produce 2-nitro-4-methoxytoluidine (I). This compound is then oxidized with potassium permanganate to give 2-nitro-4-carboxyaminobenzoic acid (II). Other derivatives synthesized include p-nitro-o-acetylsalicylic acid (III), ethyl p-acetylamidosalicylate (IV), and ethyl p-N-nicotinamidosalicylate (V), each of which is generated through specific reactions involving acetic anhydride, acetyl chloride, nicotinic chloride, and other reagents. The study also discusses esters of methionine and other specific amino acids, which react with crystalline chymotrypsin to form peptides, highlighting potential relevance to biological peptide synthesis. The study details the synthetic procedures and properties of the resulting compounds, and provides yields and melting points for each derivative, demonstrating chemical transformations and their analytical significance.
10.1021/jm0612158
The study investigates the development of a new series of spirodiketopiperazine derivatives for their cytotoxic potential against various human tumor cell lines. The researchers synthesized these compounds by condensing the 3-amino-3(ethoxycarbonyl)-2,3-dihydrothieno[2,3-b]naphtho-4,9-dione system with various amino acids, followed by intramolecular lactamization. The study evaluated the cytotoxic activity of these derivatives against MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines, revealing that certain isomers derived from Proline (Pro), Cysteine (Cys), and Methionine (Met) exhibited cytotoxic potency comparable to or greater than that of doxorubicin. The study also explored the topoisomerase II inhibition activity and DNA-binding properties of these compounds. The results suggest that these derivatives could potentially circumvent multiple-drug resistance mechanisms and have significant cytotoxic effects on various tumor cell lines, including those resistant to doxorubicin and cisplatin.
