Structural features of N-acylcytisines

Abstract

747.945+547.79+548.737 G. Genzhemuratova, M. G. Levkovich, and Kh. M. ShakhidoyatovN-Acyl cytisine derivatives were synthesized by acylation with acetic anhydride; benzoyl and o-bromo-and p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The structures of the synthesized compounds were studied using IR, PMR, and x-ray structure analysis (XSA). PMR spectra of the N-acylcytisines in solution typically had two rotational isomers around the N12-CO bond. Conformational analysis was performed using XSA for the position of the acyl group relative to the cytisine core. Bond lengths and angles of the acyl groups involved in the conjugation were analyzed.The broad spectrum of biological activity of cytisine (1) and its derivatives [1, 2] makes them a promising class for practical application. On the other hand, the chiral 3,7-diazobicyclo[3.3.1]nonane skeleton is interesting for studying structural features of substituted cytisines [3][4][5][6]. Until now, a large number of cytisine derivatives with various groups on the N atom have been synthesized [7][8][9][10][11][12], including acryloyl groups [13], thiazoles, benzthiazoles [11], and 1,2,4-thiadiazole groups [12]. In continuation of our research on transformations of 1 [11,12] and in order to find biologically active compounds in this series, we synthesized acyl derivatives via acylation of 1 with acetic anhydride and acid chlorides. The acylating agents were acetic anhydride; benzoyl-and o-bromo-and p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The reaction with acetic anhydride occurred with an excess of it. Acylation by the acid chlorides occurred in anhydrous toluene under reflux: R = -ÑH 3 (2); -Ñ 6 H 5 (3); -Ñ 6 H 4 -Br-o (4); -C 6 H 4 -NO 2 -n (5); -CH=CH-C 6 H 5 (6); -CH=CH-CH 3 (7) Acylation of 1 by acid chlorides was carried out without a HCl acceptor. Atom N12 of ring C played this role. Structures of 2-7 were confirmed by IR and PMR spectra and by an x-ray structure analysis (XSA) for N-o-bromobenzoylcytisine (4), N-p-nitrobenzoylcytisine (5), and N-crotonylcytisine (6).IR spectra contained absorption bands at 1643-1653 cm -1 (ν CO ) and 1634-1647 (ν CO ). The physicochemical properties of 2, 3, and 7 agreed with those published. PMR spectra of the N-acylcytisines in solution characteristically showed several rotational isomers around the N12-CO and CO-R bonds. They could produce spectra of several conformers or simply give very broad spectral lines because the barriers to rotation were small. In several instances resonances could not be unambiguously assigned.

Amines, Amides, and Thio- and Carboxamides of (–)-Cytisine as Nfat Transcription Factor Modulators

“…Two-dimensional 1 H-1 H COSY, 1 H-13 C HSQC, 1 H-13 C HMBC, and 1 H-1 H NOESY spectra were recorded using standard multi-pulse sequences of the instrument software. Physicochemical constants of 2, 3, 6, and 10-23 agreed with the published values [9,10,[12][13][14][15][16][17][18].…”

Cytisine as a scaffold for ortho-diphenylphosphinobenzenecarboxamide ligands for Pd-catalyzed asymmetric allylic alkylation

“…The 31 P EXSY spectra of ligands 3 ( Figure 4) showed exchange between A-chair and B-chair, as well as between A-chair and A-boat conformers and between B-chair and B-boat conformers. The preferred conformer observed by 1 H NMR in CDCl 3 solution at -20°C was the B-chair, which is in accordance with previously reported X-ray structure of analogous compounds [19]. In the case of ligand 7 the 31 P EXSY spectra showed exchange between major A-chair and minor Bchair conformers ( Figure 5).…”

Search for (-)-cytisine derivatives as potential inhibitors of NF-κB and STAT1

“…1). 12 N methylcytisine, benzilcytisine and benzoilcytisine (2)-(4), and compounds (10) and (11) were synthesized according to published method ologies [8,[33][34][35][36][37]. Derivation of compounds (5)- (9) and (12)- (22) has been described previously [38][39][40][41].…”