Spermexatin and spermexatol: new synthetic spermidine-based siderophore analogs

Abstract

Syntheses of hexanediamine-based dihydroxamate (Hexamate), spermidine-based trihydroxamate (Spermexatins), and spermidine-based mixed siderophore analogues (Spermexatols) are described. Key intermediates include the N-hydroxysuccinimide esters of various hydroxamic acids, e.g., malonohydroxamate, succinohydroxamate, and glutarohydroxamate. These intermediates were synthesized, characterized, and incorporated as the ligating chains on spermidine. Also, mixed iron chelating compounds (Spermexatols) with both catechol and hydroxamic acid side chains were synthesized. The reagent carbobenzoxyimidazole was employed to distinguish between the primary and secondary amino groups of spermidine. The ability of these iron chelators to stimulate microbial growth is also described.

Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase

“…1 H NMR (300 MHz, MeOD) d 2.14 (t, J ¼ 6.19, 2H, CH 2 NHTrt), 2.64 (t, J ¼ 6.26, 2H, CH 2 NH 2 ), 7.19 (m, 3H, para-PhH ), 7.29 (m, 6H, meta-PhH ), 7.5 (m, 6H, ortho-PhH ). 13 [11] Benzyl chloroformate (19.92 g, 117.23 mmol) was cooled to 0 C in an ice bath. Imidazole (15.96 g, 234.47 mmol) in DCM (70 mL) was added slowly.…”

“…Diamino uracil acetamides 11a and 11b were synthesised as shown in Scheme 3. The first step was selective protection of the terminal amino functions of the starting linear triamines which was carried out using carbobenzyloxy imidazole (CbZimidazole) [11]. CbZ-imidazole was synthesised from the reaction of CbZeCl with imidazole at 0 C. In the case of compound 9a, the uracil acetamide was synthesised from the reaction of compound 1 with the protected triamine 7a using dicyclohexylcarbodiimide (DCC) as a coupling reagent and 3-hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazine (DhbtOH) as an additive [12].…”

New antimalarial and cytotoxic 4-nerolidylcatechol derivatives

“…1) were prepared from 1 (401.0 mg, 1.3 mmol) by treatment with C 6 H 5 CH 2 Br (432.0 mg, 2.5 mmol, 2 equiv), K 2 CO 3 (705.4 mg, 5.1 mmol, 4 equiv), KI (22.3 mg, 0.1 mmol), and DMF (2.4 mL) for 20-30 min under N 2 (adapted from [17,18]). The reaction was stirred at room temperature for 18 h and then filtered.…”

Synthesis of optically pure chrysobactin and immunoassay development

“…2,3-Dibenzyloxybenzoic acid (Sharma et al 1989) (2, 1.34 g, 4.00 mmol) was converted to 2,3-dibenzyloxybenzoic acid-N-hydroxysuccinimide ester using N,N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide by the method described previously (Chimiak & Neilands 1984). The Nhydroxysuccinimide ester in 8 ml THF was added to a solution of e-N-Cbz-D-lysine (Aldrich, 1.12 g, 4.00 retool) in 80ml THF, 32ml H20 and 2.4ml (17 retool) triethylamine.…”

“…c~-N-(2,3-dibenzyloxybenzoyl)-e-N-Cbz-D-lysine (3) was prepared as described previously (Chimiak & Neilands 1984, Persmark et al 1989, Sharma et al 1989). In the key coupling process, N-hydroxysuccinimide ester of lysine derivative 3 was preformed using N,N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide in THF, and then coupled to L-serine benzyl ester in a mixture of organic and aqueous solvents buffered with bicarbonate ( Figure 1).…”