Z-and E-conformers of N-chloroacetylcytisine

Abstract

547.94+547.945 V. A. Saprykina, and Kh. M. ShakhidoyatovN-Chloroacetylcytisine was synthesized by acylation of (-)-cytisine. Stable Z-and E-conformers with respect to rotational isomerism around the N-12-CO bond were found in PMR spectra at room temperature. The point at which PMR resonances of the Z-and E-conformers coalesced upon heating was measured. The transition barrier between the conformers was estimated.Structural features of cytisine derivatives have recently become very significant [1][2][3][4][5]. Cytisine itself has an exceedingly rigid and sterically constrained structure that is well-known, e.g., from x-ray data. However, we encountered a strange phenomenon in PMR spectra of acylated cytisines. Certain spectral lines were doubled whereas some disappeared from the spectrum [1]. The PMR spectrum displayed temperature dependence typical of spectra of molecules with several conformations of similar energy. This provided an impetus, along with the previous results [1], to study the stereochemical dynamics of acylated cytisine derivatives.In continuation of research in this area, we studied the reaction of (-)-cytisine and chloroacetylchloride. The reaction was carried out without an HCl acceptor and also in the presence of pyridine (Py) or Et 3 N. The yield of N-chloroacetylcytisine without an HCl acceptor was only 35%. The reaction in Py gave the target product in 77.6%. The yield of the final product was better (98%) for reaction of the (-)-cytisine:ClCH 2 COCl:Et 3 N in a 1:1.2:1.2 ratio in CHCl 3 at room temperature.An analysis of the PMR spectrum of N-chloroacetylcytisine (1) in DMSO-d 6 at room temperature showed that most resonances in it were doubled. The reason for this doubling was the well-known rotational isomerism around the N-12-CO amide bond [1,4,6]. Conjugation of the carbonyl with the planar N atom leads to two rotational conformations that are designated [4] as the Z-and E-conformers.A series of N-acylcytisines that also showed Z-and E-conformers in the PMR spectra has been reported [1]. However, spectra were recorded in CHCl 3 at room temperature in that work, i.e., under conditions where a large number of very broad and overlapping resonances was observed. This did not allow several resonances to be assigned. Also, the samples could not be heated to the coalescence point and the barrier height could not be estimated because of the low boiling point of CHCl 3 .Herein we report spectra of 2 in DMSO-d 6 in the temperature range from ambient to 150°C. Table 1 lists the assignments of resonances with SSCC at room temperature. Figure 1 shows the PMR spectrum of 2 at room temperature and +150°C.

Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates

“…There is one set of C resonances in CDCl 3 at room temperature. After replacement of N(3)-H with NPC , two sets of the 1 H ( Figure 2 A) and 13 C resonances ( Figure 3 ) are observed, corresponding to E - and Z -conformers or chair( syn ) and boat( anti ) isomers similar to that for other N -acyl derivatives [ 25 , 26 ]. Due to the presence of the aromatic ring of the NPC substituent, the magnetic nonequivalences of 2-, 4-, and 6-CH 2 protons are observed with ca.…”

“…C is an alkaloid originating from some plants [24] and is used to treat nicotine addiction [21]. It can be easily converted into N-acyl derivatives by reaction with acyl chlorides [25,26]. We have obtained the N-(p-nitrophenyl)carbonate derivative (CNPC) and characterized it by 1 H and 13 C-NMR spectroscopy.…”

Semisynthesis of novel N‐acyl/sulfonyl derivatives of 5(3,5)‐(di)halogenocytisines/cytisine and their pesticidal activities against Mythimna separata Walker, Tetranychus cinnabarinus Boisduval, and Sitobion avenae Fabricius

“…Yield: 92%, white solid, m.p. 190–192 °C [literature, 198 °C]; [α] 25 D = −58 ( c 2.5 mg mL −1 , CHCl 3 ); IR cm −1 (KBr): 3023, 2945, 2905, 1644, 1571, 1543, 1462, 1362, 1090, 801; 1 H NMR (500 MHz, CDCl 3 ) δ : 7.30 (dd, J = 9.0, 6.5 Hz, 1H, H‐4), 6.48 (d, J = 9.5 Hz, 1H, H‐3), 6.09 (t, J = 5.5 Hz, 1H, H‐5), 4.74 (d, J = 13.5 Hz, 0.45H), 4.63 (d, J = 13.0 Hz, 0.53H), 4.30 (d, J = 16.0 Hz, 0.53H), 4.11 (d, J = 16.0 Hz, 0.47H), 3.93–4.01 (m, 1.54H), 3.85–3.89 (m, 1.47H), 3.73 (br, s, 1H, H‐7), 3.50 (dd, J = 12.0, 10.5 Hz, 1H), 3.13 (br, s, 1H, H‐7), 2.95 (t, J = 15.5 Hz, 1H), 2.58 (br, s, 1H, H‐9), 2.01–2.09 (m, 2H, H‐8); 13 C NMR (125 MHz, CDCl 3 ) δ : 166.0, 165.8, 163.2, 163.1, 147.97, 147.93, 139.1, 138.5, 118.1, 117.6, 105.9, 105.1, 53.4, 52.1, 49.2, 48.7, 48.3, 40.4, 40.1, 34.8, 34.2, 27.5, 27.3, 26.0; HRMS (ESI): Calcd for C 13 H 16 N 2 O 2 Cl ([M+H] + ), 267.0894; Found, 267.0895.…”

Voltammetric Analysis of Licochalcone A in Licorice

“…Concerning its analytical determination not many methodologies can be found in literature and there are mainly chromatographic methodologies, either by high-performance liquid chromatography 23,24 or high-speed counter-current chromatography, 1 both with spectrophotometric detection. To the best of our knowledge no electroanalytical methodologies have been developed for licochalcone A.…”