Acylation of Convolvine by Anhydrides of Mono- and Dicarboxylic Acids

Abstract

The alkaloid contents of Convolvulus subhirsutus and C. pseudocanthabrica growing in various regions of Uzbekistan, Kazakhstan, and Tadzhikistan were previously investigated and were found to include ~10 tropane alkaloids [1,2]. The alkaloid composition and content depended on the habitat. Thus, total alkaloids in C. subhirsutus growing in Uzbekistan was 0.6-0.75% (aerial part) and 0.6-1.6% (roots) [2,3]; in Tadzhikistan, 0.12%(aerial part) [4]. The main alkaloids in all plants were nortropine derivatives convolvine (1, 3,4-dimethoxybenzoyloxynortropane) and convolamine (3,4-dimethoxybenzoyloxytropane), which amounted to 40-50% of the total.The alkylation and acylation of the NH group in 1 were studied [3]. Preliminary tests showed that the synthesized compounds included some with pronounced antihypoxic, immunomodulating, and anti-inflammatory activity. Therefore, it seemed interesting to synthesize other derivatives of 1.The present work communicates results from the reaction of 1 with aliphatic (acetic, propionic, butyric), aromatic (benzoic), and cyclic (succinic, glutaric) anhydrides. It was expected that the NH group would be acylated. Also, transacylation of the 3,4-dimethoxybenzoic moiety to form new O-acylated derivatives was possible. The reaction was carried out in anhydrous benzene. Acylation by acetic, propionic, butyric, and benzoic anhydrides occurred at room temperature. Heating to 70-80°C was required for succinic and glutaric anhydrides. The first four anhydrides produced N-acetyl-(8), -propionyl-(9), -butyryl-(10), and -benzoylconvolvines (11).The reaction with the cyclic anhydrides (6 and 7) formed N-Z-carboxyalkyl)-convolvines (12 and 13). The free carboxylic acid did not react further.The course of reactions was monitored by HPTLC (high-performance TLC). The structures of the synthesized compounds were proved using UV, IR, and PMR spectroscopy.IR spectra of 8-13 showed that the NH absorption band of starting convolvine at 3387 cm -1 disappeared and an absorption band of the N-CO fragment at 1622-1699 cm -1 appeared. The COO ester absorption band was found at 1698-1705 cm -1 .PMR spectra of 8-13 showed that the chemical shifts of the aromatic, methoxy, and methylene protons practically did not change whereas the methine protons associated with the N atom (H-1, 5) appeared as triplets and multiplets (for 8-10, 12,