Synthesis of New Pyrazole–Methylmaleopimarate Conjugates

Abstract

Regiospecific synthesis of conjugates containing a diterpenoid fragment and a pyrazole-ring pharmacophore by 1,3-dipolar cycloaddition of diazomethane to allenoates in the presence of Et 3 N was demonstrated.Pyrazoles are very important heteroaromatic compounds due to their broad distribution in natural products and pharmacologically active compounds [1-3]. Many pyrazole-containing compounds such as Celebrex [4], rimonabant [5], and Viagra [6] were successfully commercialized as drugs. Methyl maleopimarate (MEMPA) was obtained by the known method from levopimaric acid and maleic anhydride [7,8] and is a convenient and available reagent for synthesizing compounds with anti-inflammatory, antiulcer, fungicidal, and other activities [9][10][11][12]. In continuation of research on potential biologically active compounds, we synthesized conjugates with a diterpene fragment and pyrazole-ring pharmacophore. The key reaction was 1,3-dipolar cycloaddition of diazomethane to allenoates.Allenes 4a-c were synthesized from N-substituted amino acids 2a-c, which were obtained via condensation of MEMPA (1) with glycine, E-alanine, and J-aminobutyric acid in refluxing DMF. The reaction of N-substituted amino-acid chlorides 2a-c with Et 3 N passed through ketenes 3a-c, which reacted with methyl(triphenylphosphoranylidene)acetate to give allenoates 4a-c in yields of 63, 67, and 70%, respectively [13] (Scheme 1). The structures of the synthesized allenes were proved by physicochemical analytical methods. Thus, 13 C NMR spectra were characterized by resonances for two terminal allene C atoms C-2c and C-4c at G 96.13 and 91.17 ppm for 4a; 90.16 and 89.7 ppm, 4b; 91.86 and 88.56, 4c; and also central C atom C-2c at G 210.37 ppm for 4a; 212.89, 4b; and 212.44, 4c.

Kinetic study of the reaction of nucleophilic cyclopropanation of C60 fullerene with halogenated maleopimarimide

“…In conformity with the formulated goal and its solution, methane fullerenes with maleopimarimide fragments, which were not described in the scientific literature, have been chosen as test compounds. The synthesis of chloro‐ 3a–d and bromomethyl ketones 4a–d has been carried out on the basis of the previously obtained N ‐maleopyrimarimide‐substituted carboxylic acids 1a–d . Linear amino acids as starting ones were further converted into the spacer element, with the length of the carbon chain from n = 1 to n = 5.…”

Synthesis of 1,2,3-Triazole Derivatives from 2,3-Dienoates of Methyl Maleopimarate

“…Its physicochemical characteristics agreed with those in the literature. Acid 2 and allenes 4a-d were prepared by the described method [6]. Methyl-2-azidoacetate was synthesized as before [10].…”