Synthesis, characterisation and anti-protozoal activity of carbamate-derived polyazamacrocycles

Abstract

A short, highly efficient approach for the synthesis of a novel class of polyazamacrocycles containing N-functionalised carbamate side-chains has been developed. The key steps involved a phase-transfer mediated macrocyclisation to form the ring system as well as a tin-catalysed reaction with isocyanates to introduce the carbamate side-chains. X-Ray crystallography confirmed successful formation of the 1,4,7,10-tetraazacyclododecane ring and N-functionalisation of all the amine centres. Preliminary testing of the biological activity of the compounds revealed significant anti-parasitic activity against bloodstream form African trypanosomes.

Synthetic Strategies TowardN‐Functionalized Cyclens

“…or 70 % ref 11, . 9a → 1 in ref 16. HBr, phenol, AcOH, reflux, 46 %, 9c → 10b , i : HCOH, HCOOH, 110 °C, ii : Red‐Al, PhCH 3 , 100 °C, 10 % (based on 9c ), 9d → 10c , i : Na, NH 3 (l), ii : ClCH 2 COOH, NaOH, H 2 O, iii : H 2 , Pd/C, MeOH, authors14 claim low yield, no exact value reported.…”

“…Considering that cyclen ( 1 ) is commercially available for a reasonable price from multiple suppliers it is rather surprising that the labor intensive 3+1 cyclization strategy to form cyclen is still in use 16. Stirring (5 d) of the precursors 7a and 8a in DMF at room temperature in the presence of Cs 2 CO 3 afforded N 1 , N 4 , N 7 , N 10 ‐tetratosylcyclen ( 9a ) in 79 % yield (Scheme ).…”

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

“…The last mentioned modification employed reaction of 1,4,7,10-tetrakis(p-toluenesulfonyl)-1,4,7,10-tetraazadecane with 1,2-dibromoethane in DMF using potassium carbonate as a base. Probably the most efficient modification of the Richman-Atkins procedure is the reaction of 1,4,7-tris(p-toluenesulfonyl)-1,4,7-triazaheptane with O,N,O -tris(p-toluenesulfonyl)diethanolamine in presence of LiOH as a base [144][145][146], as shown in Scheme 3.32.…”

A copper–cyclen coordination complex associated with a polyoxometalate anion: Synthesis, crystal structure and electrochemistry of [Cu(cyclen)(MeCN)][W6O19]

“…The major difficulty in isolating such crystalline materials lies in the fact that, very often the physical mixture of the components ends up with an immediate formation of precipitate that inhibits complete characterization of such synthesized materials. Our preliminary investigation on coordination complexes of tetra-aza-crown ethers associated with POM anions has prompted us to synthesize an ion-pair compound [Cu (cyclen)(CH 3 CN)][W 6 O 19 ] (1) through a slow diffusion technique.Various synthetic routes/strategies have been developed, so far, to obtain cyclen in small to bulk quantities [31][32][33][34]. We have taken up one of them.…”

“…Various synthetic routes/strategies have been developed, so far, to obtain cyclen in small to bulk quantities [31][32][33][34]. We have taken up one of them.…”