Benzimidazole-5(6)-alanine and related compounds. I. Synthesis of amino acids as inhibitors of norepinephrine biosynthesis

Abstract

Ethyl -Phthalimidoocetoacetate Ethylene Thioketal.-Ester II (5 g, 0.018 mol) and 2.7 g (0.028 mol) of ethanedithiol were dissolved in CHC13 and 5.8 ml of BF3-etherate was added. The solution was stirred 3 hr at 25°, then was washed with NaHCOg solution, dried, and concentrated. After long standing it partly crystallized from ¿-Pr20, 3.1 g, mp 71-72°. Anal. (CieHuXOJSa) C, , N, S.Pyrrolidine-2,4-dione 4-Ethylene Ketal (XIV).-NaOMe (0.32 g, 0.006 mol) wTas added to a solution of 2 g of XI (0.006 mol) and 0.23 g (0.007 mol) of NH2OH in MeOH. The solution turned pale yellow', then bright yellow, orange and, after 15 min, red. Shortly afterwards a solid precipitated. After 16 hr, the solid Xa salt of Ar-hydroxyphthalimide (0.6 g) was filtered, the filtrate was diluted with a large volume of i-Pr20 and more Na salt (0.25 g) was removed. The filtrate was concentrated giving 1.5 g of crude XIV, as an oil. This material slowly recrystallized and was then sublimed in vacuo and recrystallized from f-Pr20, to give 0.7 g of XIV, mp 98-101°. The compound shows a typical lactam absorption in the ir at 5.92 µ. Anal. (CeHgNOs) C, , N.

Synthesis and biological activity of DL-3-(5-benzimidazolyl)-2-methylalanine

“…iV-Acetyl-2-methyl-3-phenyl-DL-alanine methyl ester (1) was nitrated, reduced, and acetylated to yield Ar-acetyl-3-(4-acetylaminophenyl) -2-methyl-DL-alanine methyl ester (3). Nitration of 3, followed by hydrolysis, reduction, and cyclization, gave the title compound MBA ( ).…”

“…Because of their environmental occurrence, high activity, and often application-independent, organospecific effects, nitrosamines have gained broad application and worldwide interest for practical and mechanistic studies in cancer and mutagenesis research; the alkylation hypothesis of carcinogeneity requires that they are hydroxylated enzymatically to give, for instance, 1 (X = OH) which is a potential precursor of alkylating diazonium ions and/or diazo compounds. [1][2][3][4] In order to further test this theory, new methods of preparation of a-heteronitrosamines were desirable. Hitherto, only ethers of type 1 (X = OR) were readily available.…”

New Antibacterial Peptide Analogs of 5-Aminobenzimidazoles

“…Although pharmacological importance of benzimidazoles is well established, but there are very few reports available on the synthesis of their peptide analogs. Synthesis of 3-(1H-benzimidazol-5-yl)alanine derivatives is reported by condensation in solution, 16,17 another approach is by alkylation of glycinate, 18 while Wittig reaction of aldehyde and protected phosphonoglycine for the same purpose is also attempted. 19 Recently solid phase synthesis has also been exploited to prepare derivatives of 3-(1H-benzimidazol-5-yl)alanylglycine.…”

Expedient on-resin synthesis of peptidic benzimidazoles

“…Generally, the synthesis of amino acids containing benzimidazole functionality proceeds via solution-phase reduction of a 3-nitro-4-aminophenylalanine 35 or similar di-nitro compound 36 with subsequent heating in acetic acid to induce dehydration. This strategy has been adapted for solid phase peptide synthesis using Fmoc-protected 3-nitro-4-aminophenylalanine and on resin reduction with tin(II) chloride, followed by condensation of the diamine onto a range of aldehydes.…”