Convolinine, a new alkaloid from Convolvulus subhirsutus of Uzbekistan flora

Abstract

957.944/945 M. G. Levkovich, and O. AripovSeveral alkaloids of known structure and the new base convolinine were isolated from total alkaloids from the aerial part of Convolvulis subhirsutus growing in Uzbekistan. It has been established that convolinine is an N-hydroxyethyl derivative of convolvine and has the structure (±)-3D-(3,4-dimethoxybenzoyl)-Nhydroxyethylnortropane based on spectral data and an x-ray crystal structure. ) were isolated from the aerial part of Convolvulus subhirsutus growing in Uzbekistan [1,2]. In continuation of the study of C. subhirsutus roots collected in Tashkent Oblast, a new alkaloid (mp 128-129°C, [D] D 0°) was isolated from total alkaloids of the non-phenolic part after isolation of convolvine and convolamine by column chromatography over Al 2 O 3 of the mother liquor of the non-phenolic part of total bases from the benzene:CHCl 3 fractions. The physicochemical properties and chromatographic mobility differed from those described in the literature for tropane bases. We called it convolinine (1).The alkaloid had the formula C 18 H 25 NO 5 . The IR spectrum of the base contained absorption bands for active H at 3290 cm -1 ; ester carbonyl, at 1749; 3,4-disubstituted benzene, at 1601, 1516, 878, and 821; stretching and bending vibrations of CH 3 -, CH 2 -, and CH-, at 29222 -, and CH-, at , 28542 -, and CH-, at , 14632 -, and CH-, at , 14192 -, and CH-, at , 12842 -, and CH-, at , and 1274; and ether -C-O-C-, at 1074 and 1021.The PMR spectrum exhibited resonances for protons of two aromatic methoxyls as two 3H singlets at 3.87 and 3.89 ppm. An 8H multiplet was found in the range 1.85-2.85 that is characteristic of tropane bases for four CH 2 groups of a tropane ring in the C-2, C-4, C-6, and C-7 positions. A 2H multiplet probably for CH 2 protons bound to a N atom was observed at 3.77. A 2H multiplet for two methine protons of C-1 and C-5 in a tropane ring that is characteristic of tropane alkaloids occurred at 3.59. A 1 H triplet for H 3E that is diagnostic for tropane bases esterified on the C-3 hydroxyl was located at 5.23. Resonances for three aromatic protons with characteristic structure of meta-and para-substitution were seen at 7.60-6.80. The isolated D-proton appeared as a doublet with J = 2.0 Hz at 7.50. The other aromatic -proton gave a doublet of doublets (meta-constant J = 2.0 Hz and ortho-constant J = 8.5 Hz) at 7.58. Finally, the E-proton resonated at 6.84 as a doublet (J = 8.5 Hz). A 2H multiplet for protons of CH 2 bonded to oxygen was noted at 2.75.Based on these spectral characteristics, IR spectra (absorption bands for active H), PMR spectra, and taking into account the molecular weight of the alkaloid (M + 335) with an unsubstituted N-containing tropane core, it can be hypothesized that convolinine has a substituted N atom and that the substituent is -C 2 H 4 OH. The PMR spectra suggest that this could be a -CH 2 -CH 2 -OH group on the N atom.

Stereochemistry of tropane alkaloid of convolvine and their derivatives

“…The substituent the veratroyloxy group in position C3 has an α-axial orientation relative to the tropane core. The orientation and location of the substituents of the N and C3 atoms in compounds 1, 2 and 3 coincides with those observed in convolinine [8] and o-benzoyltropine hydrochloride [9]. In molecules 1-3, the veratroyloxy group is planar with an accuracy of ±0.040, ±0.039 and ±0.036 Å, respectively, and the benzyl group at N1 in 3 is ±0.008 Å.…”

“…(3) The veratroyloxy group is distorted from the plane of symmetry of the tropane core, which is characterized by the torsion angle H3-C3-O1-C1', whose values for compound 1-3 are 33, 29 and 33°, respectively. It should be noted that the carbonyl group in these compounds and analogues known in the literature [8][9][10][11][12] is always syn-directed relative to the β-axially located hydrogen atom at C3. But the methoxyl group in the ortho position of the C3' veratroyloxy fragment in these compounds is located differently relative to the tropine core (Figure 1), which indicates a free rotation around the C16-C1' bond forming different rotamers.…”

Synthesis of convolinine and cytotoxic activity of alkaloids of the genus Convolvulus and their derivatives

“…Because convolinine (3) is a minor alkaloid of C. subhirsutus [6], it was synthesized from convolvine in order to study its cytotoxic properties. Its content in C. subhirsutus is 0.25-0.35% of the air-dried raw material mass [3].…”

“…Its content in C. subhirsutus is 0.25-0.35% of the air-dried raw material mass [3]. The reaction of 1 and ethylenechlorohydrin (6) in the presence of Et 3 N produced 3, which was identical to the natural alkaloid convolinine according to spectral properties (see Experimental 1: R 1 = H, R 2 = CH 3 ; 2: R 1 = R 2 = H; 3: R 1 = CH 2 CH 2 -OH, R 2 = CH 3 4: R 1 = CH 2 C 6 H 5 , R 2 = CH 3 ; 5:…”