The review integrates data on the synthesis of chiral oxygen-containing heterocycles of various structural types by reactions of monoterpenoids with carbonyl compounds. Depending on the structure of the monoterpene and carbonyl components and the catalyst used, these reactions lead to mono-, bi-, tri- or tetracyclic products. The possible reaction mechanisms are discussed and data on the biological activities of the products are given.
The bibliography includes 125 references.
We previously showed that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2yl)cyclohex-3-ene-1,2-diol 1 alleviates motor manifestations of Parkinson's disease in animal models. In the present study, we designed and synthesized monoepoxides of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 and evaluated their biological activity in the MPTP mouse model of Parkinson's disease. We also assessed the ability of these compounds to penetrate the blood brain barrier (BBB). According to these data, we choose epoxide 4, which potently restored locomotor activity in MPTP-treated mice and penetrated the BBB with high efficacy, to further explore the potential mechanism of action. Epoxide 4 was found to robustly promote the survival of cultured dopamine neurons, protect dopamine neurons from toxin-induced degeneration and trigger the mitogen-activated protein kinase (MAPK) signaling cascade in cells of neuronal 2 origin. Meanwhile, neither survival-promoting effect nor MAPK activation was observed in nonneuronal cells treated with epoxide 4. In the MPTP mice model of Parkinson's disease, compound 4 increased the density of fibers expressing the key enzyme of dopamine synthesis, tyrosine hydroxylase. Taken together, these data indicate that epoxide 4 can be a promising compound for further development not only as symptomatic treatment but also as a disease-modifying drug to treat Parkinson's disease.
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