A green synthesis in water of novel (1,5,3-dithiazepan-3-yl)alkanoic acids by the multicomponent reaction of amino acids, $$\hbox {CH}_{2}$$ CH 2 O, and 1,2-ethanedithiol

Abstract

A library of new (1,5,3-dithiazepan-3-yl)alkanoic acids was prepared by the multicomponent cyclocondensation of amino acids, formaldehyde, and 1,2-ethanedithiol in water at room temperature for 1 to 5 h in high yields. This green procedure offers several advantages such as an operational simplicity, no catalyst, and no production of hazardous materials.

Multicomponent Polymerization toward Cationic Polymers for Efficient Gene Delivery

“…In 2014, Akhmetova and co‐workers developed a catalyst‐free three‐component reaction of amine, formaldehyde, and thiol toward the sulfur‐ and nitrogen‐containing compounds. [ 48,49 ] Inspired by such MCR, in this work, we disclosed a new three‐component polymerization starting from dithiol, formaldehyde, and di‐ sec ‐amine to access a library of polycations containing both thioether and tertiary amine groups (a). To best of our knowledge, PEGylation of the polycations could partially shield the cationic charges and improve the serum stability by the hydrophilic corona, which is an efficient strategy to minimize the in vivo toxicity.…”

Intermolecular interactions and chiral crystallization effects in (1,5,3-dithiazepan-3-yl)-alkanoic acids

“…Moreover, the stereoelectronic effects and interactions in N-C-S, N-N-C, and lp-S-C-NH + systems of the related compounds were revealed. 25 A search in the Cambridge Structural Database has shown a wide variety of the compounds involving N-OH and amino acid fragments (Table S1, ESI †). 1).…”

Efficient synthesis of N-carboxyalkyl-substituted dithiaza- and dioxadithiazacycloalkanes by cyclocondensation of amino acids with formaldehyde and α,ω-dithiols

“…Recently we reported on the synthesis of (1,5,3dithiazepan-3-yl)alkane acids by cyclocondensation of amino acids with formaldehyde and 1,2-ethanedithiol [14,15]. Heterocyclic derivatives of amino acids participate in many vital biological processes and find application in modern pharmacology [16][17][18][19] and food industry [20][21][22], cattle breeding and veterinary [23], in agriculture for protecting plants from various diseases [24].…”

“…Glycine enters in the reaction of [1+2+1]-cyclocondensation with formaldehyde and α,ω-dithiols (1,3-propane-or 1,4-butanedithiol) at room temperature (Scheme 1) in a molar ratio 1 : 2 : 1 with the formation of N-carboxymethyl-substituted 1,5,3-dithiazocane 1а or 1,5,3-dithiasonane 1b in conditions described for the reaction of amino acids with formaldehyde and 1,2-ethanedithiol (20°С, H 2 O [14]). 1,5-Pentanedithiol in these conditions furnishes a mixture of reaction products.…”

“…According to the data of 2D NMR (HSQC, HMBC, 1 Н-15 N-HMBC, COSY, NOESY), the signals of hydrogen and carbon atoms of the methylene group СН 2 СН 2 N in 1 Н and 13 С NMR spectra overlap the signals of methylene group of the fragment (SCH 2 ) 2 CH 2 at 1.87 and 22.3 ppm respectively. The upfield shift of signals of methylеne group located in the α-position from the nitrogen atom of the substituent (СН 2 СН 2 N), compared with the neutral 3-(1,5,3-dithiazepan-3-yl)propanoic acid [14], is evidently due to the protonation of nitrogen atom at the formation of hydrochloride or hydrobromide [25]. The cyclocondensation of amino acids with 3,6-dioxa-1,8-octanedithiol and CH 2 О in molar ratio 1 : 2 : 1 in water at room temperature (20°С) occurs ambiguously.…”