Syntheses and Properties of [1,1′-Bis(α-Aminoisobutyric Acid)]Gramicidin S and [1-α-Aminoisobutyric Acid]Semigramicidin S

Abstract

Analogs of gramicidin S, [1,1′-bis(α-aminoisobutyric acid)]gramicidin S (18) and [1-α-aminoisobutyric acid] semigramicidin S (11), have been synthesized by a conventional solution method. The cyclization reactions of a linear pentapeptide active ester and a linear decapeptide active ester yielded exclusively a protected cyclic pentapeptide and a protected cyclic decapeptide, respectively. After deprotection of these peptides, we obtained the final products (11 and 18). The mobility of 18 in paper electrophoresis was the same as that of gramicidin S, however, the CD spectrum of 18 in a methanol solution showed a markedly different pattern from that of gramicidin S. Both analogs (11 and 18) are inactive against the Gram-positive microorganisms tested. The results suggest that the positions of the valine residues in gramicidin S require a hydrophobic amino acid having l-configuration to show activity.

Aminodecalone Scaffolds – Enantioselective Synthesis, Indole and Quinoline Annulation

“…The nitro group of compound 22 was then reduced with Zn–AcOH to the primary amino function, however, this material turned out to be difficult to purify. Nevertheless, it could be further amidated with N ‐Boc aminoisobutyric acid (Aib) using COMU {[(1‐cyano‐2‐ethoxy‐2‐oxoethylideneaminooxy)(dimethylamino)morpholino]carbenium hexafluorophosphate} as coupling reagent and NEt 3 as base, furnishing the target amide 23 (56 % yield).…”

“…GLC analyses were performed on a GC‐2010 Plus (Shimadzu) on a Lipodex E capillary column (Macherey–Nagel, 30 m, 0.25 mm) with H 2 as carrier gas. l ‐Valine diethylamide and N ‐Boc Aib were literature known and prepared according to published procedures. All other starting materials were commercially available.…”

Investigation into a Tetrahydroquinazoline Scaffold

“…Next, the thioether 11 c was coupled with N-Boc aminoisobutyric acid (N-Boc-Aib). [16] The yield of product 5 e (entry 5) was now significantly lower (62 %) which is probably due to steric hindrance by quaternary centers at both coupling partners. HATU coupling of two slightly electron deficient aromatic carboxylic acids gave the fluorinated benzamides 5 f and 5 g in surprisingly good yields (93 % and 99 % yield, resp., entries 6 and 7).…”

New Octahydropyrido[3,4-b]acridine Scaffolds for Combinatorial Chemistry

“…After stirring overnight, yields were generally quantitative (95-97%), except for compound 14e, which required three days to give a 60% yield of the isolated product 7e (entry 5). Three amino acid derivatives were used as carboxylic acids: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-b-alanine (Fmoc-b-Ala, entry 1), 2-[(tert-butoxycarbonyl)amino]isobutyric acid (Boc-Aib, entry 2), 22 and N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-neopentylglycine 23 (Fmoc-Npg, entry 5). Reactions with benzoic acid (entry 3) and its electron-rich derivative (entry 4) proceeded without any problems.…”

“…Octahydropyrido [3,4-b] 22 and Fmoc-Npg, 23 which were prepared according to literature procedures. Compounds 3b 7 and 3c 10 were previously reported without spectroscopic data.…”