SYNTHESIS OF TRIAZOLES AND PYRAZOLES FROM METHYL MALEOPYRIMARIMIDE SUBSTITUTED AMINO ACIDS
The 1,3-dipolar cycloaddition of diazomethane or methyl 2-azidoacetate to allenoates results in the regioselective formation of hybrid compounds containing a diterpene fragment and pharmacophore pyrazole or triazole rings, respectively. Pyrazole, a five-membered heterocycle containing two neighboring nitrogen atoms, has become one of the most important scaffolds due to its wide distribution in natural products and pharmacologically active compounds. Several pyrazole-containing compounds, such as celecoxib, rimonabant and viagra, have been successfully commercialized as drugs. Heterocyclic systems with a 1,2,3-triazole ring are also very attractive compounds in terms of their use for creating protective agents, plant growth regulators and drugs, known for their antibacterial, anti-inflammatory, antimicrobial, antitumor, anticonvulsant, antiallergic properties. In addition, maleopimaric acid, which is a Diels-Alder adduct of rosin with maleic anhydride, is considered as an important framework for the synthesis of many bioactive molecules. With this in mind, we selected methyl maleopimarate as an easily accessible starting block for the synthesis of pyrazole and triazole derivatives. Maleopimaric acid methyl ester derivatives were modified by introducing pharmacophore 1,2,3-triazole and pyrazole rings. To construct five-membered cycles, we used the reaction of 1,3-dipolar cycloaddition; for this, first, allenic compounds were obtained from the methyl maleopimarata - glycine and β-alanine condensation products. It should be noted that according to the standard method for the preparation of triazoles using an equimolar amount of azide, the triazole yields do not exceed 20%, while the use of a twofold excess of methyl 2-azidoacetate made it possible to increase the yield of the target products by more than two times. It was revealed that the interaction of CH2N2 with allenoates proceeds regioselectively with the formation of a C-N bond in the α-position to the ester group. In all cases, incomplete conversion of allenoates was observed. Thus, convenient methods have been developed for the synthesis of methyl maleopimarate derivatives containing pharmacophore triazole and pyrazole rings.