2, 3‐Bis(5‐alkyl‐2‐thiono‐1, 3, 5‐thiadiazin‐3‐yl) Propionic Acid: One‐Pot Domino Synthesis and Antimicrobial Activity

Abstract

In a search for promising antibacterial and antifungal compounds, two new series of 2, 3-bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl)propionic acid 1 and their corresponding N, N-dimethylpropionamide 6 have been synthesized. The reaction of 2, 3-diaminopropionate 3, carbon disulfide, formaldehyde, and the appropriate alkyl amines furnished the title compound 1. N, N-dimethylpropionamides 6 were obtained by the reaction of 1 with dimethyl amine in the presence of POCl(3). The newly prepared compounds were screened in vitro against certain strains of Gram-positive and Gram-negative bacteria and compared with nalidixic acid and ciprofloxacin. Moreover, the title compounds were tested for their antifungal activity in vitro against Candida albicans, phytopathogenic, Penicillum expansum and Trichoderma hazianum, and aflatoxin-producing Aspergillus flavus. These compounds exhibit varied activity against the tested pathogenic bacteria and remarkable inhibitory effects on growth or sporulation of some of the tested fungal species.

Liquid phase organic synthesis of 3,5-disubstituted 1,3,5-thiadiazinane-2-thione derivatives on polyethylene glycol (PEG) support

“…26,27 Taking into account the remarkable antiprotozoal activity exhibited by THTT, and in order to increase the molecular diversity based on the THTT motif, two THTT rings were incorporated into the same molecular structure (bis-THTT). 21,22 In this work, we have adapted our LPOS strategy of THTT derivatives to expeditious synthesis of two new hybrid structures endowed with two THTT rings, connected through their N-3 atoms by a linear aliphatic backbone (C 6 H 12 ) and tripeptide residues at N-5 (bis-THTT-tripeptide). The synthesis of the bis-THTT-tripeptides was carried out as shown in Scheme 2 through a polymeric intramolecular reaction taking advantage of the special flexibility of the PEG units.…”

“…21 Taking to account the interaction mechanism suggested for this heterocycle, the incorporation of two THTT moiety in the same structure must increase the activity of these derivatives as antiparasitic agents. 22 We have previously demonstrated the feasibility of the synthesis of thiadiazinane-2-thiones in solution [14][15][16][18][19][20][21] by reaction of the appropriate amine with carbon disulfide and potassium hydroxide, to give the dithiocarbamate potassium salt, which is not isolated, followed by cyclocondensation with formaldehyde and the selected amino acids or pseudopeptides able to provide the nitrogen atom at the N-5 position of the thiadiazinane ring. Based on experimental evidence and DFT studies, a probable cyclization route to 1,3,5-thiadiazinane-2-thiones in aqueous medium was proposed.…”

Thiourea, triazole and thiadiazine compounds and their metal complexes as antifungal agents

“…A series of 20 1,3-disubstituted aliphatic and aromatic symmetrical and unsymmetrical thioureas ( Table 1 and Scheme 1) compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were synthesized by novel routes and the antifungal activities of these compounds against two plant pathogens, Pyricularia oryzae and Drechslera oryzae were studied [3].…”

“…Further, compounds with nitro substitution completely inhibited the growth of both pathogens at 1000 mg/L. Compounds containing the o-tolyl group as the basic skeleton with substituents such as ethyl, dimethyl, cyclohexyl and phenyl moieties at position 3 (7,(11)(12)(13)(14)(15) were found to have good antifungal activity except for the o-tolyl-3-ethylthiourea compound (12). Retention of a cyclohexyl group at position 1 and a dimethyl group at position 3 maintained antifungal activity.…”

“…Thiadiazines are also efficient antibacterial and antifungal compounds [12] and their use in the treatments of the bacteria Helicobacter pylori and as reverse transcriptase inhibitors of the human immunodeficiency virus have been reported [13,14].…”