Synthesis of oxygen-containing heterocyclic compounds based on monoterpenoids

Abstract

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.

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

“…The reactants for the products with the 3-oxabicyclo[3.3.1]nonane framework 12a in reactions of the 2-carene-containing mixture with aldehydes can be both 2-and 3-carene as well as limonene and possibly terpinenes [15,23]; a proposed reaction mechanism for compounds 11, 12, and 13 is shown in possibly terpinenes [15,23]; a proposed reaction mechanism for compounds 11, 12, and 13 is shown in Scheme 3. The yields for 11, 12, and 13 were calculated based on the 2-carene concentration in the mixture and on the total concentration of carenes, limonene, and terpinenes.…”

“…It should be noted that compound 11d, in contrast to the previously studied reactions with aromatic aldehydes, the crotonaldehyde, formed exclusively as an (S)-isomer [23]. Moreover, although Prins cyclization in reactions of terpenoids with aldehydes, leading to the formation of heterocycles, with the 3-oxabicyclo[3.3.1]nonane framework is well studied [15,23], the only example of isolating a compound with an exocyclic double bond is the reaction of α-terpineol 14 with benzaldehyde in the presence of BF 3 * Et 2 O, leading to 13d [36].…”

“…Monoterpenes, which have a unique diverse structure and are inexpensive, available and often enantiomerically pure, is an attractive renewable material for the development of physiologically active agents [14]. One of the approaches to utilize various monoterpenes, such as pinenes and p-menthenes, is their capability to react with carbonyl compounds, mainly aldehydes, resulting in heterocyclic compounds of different structural types [14,15]. Some of these derivatives exhibit analgesic, antiviral, neuroprotective, and antitumor properties [14].…”

A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold

“…The most commonly used catalysts in this transformation are montmorillonite clays or Lewis acids such as Sc(OTf) 3 , BF 3 *Et 2 O, or I 2 [ 19 , 20 , 21 , 22 ]. Montmorillonite clays were also found to be effective catalysts for the synthesis of octahydro-2 H -chromenes with heterocyclic motifs [ 23 , 24 , 25 , 26 ]. Although aldehydes containing amino groups cannot be involved in such reactions because of catalyst poisoning [ 26 ], in principle, such products can be obtained through reactions with nitro-aromatic aldehydes, followed by the reduction of the nitro group.…”

“…Montmorillonite clays were also found to be effective catalysts for the synthesis of octahydro-2 H -chromenes with heterocyclic motifs [ 23 , 24 , 25 , 26 ]. Although aldehydes containing amino groups cannot be involved in such reactions because of catalyst poisoning [ 26 ], in principle, such products can be obtained through reactions with nitro-aromatic aldehydes, followed by the reduction of the nitro group. For example, we have successfully obtained nitro-containing octahydro-2 H -chromene from 5-nitro-thiophene-2-carbaldehyde in our previous work [ 18 ].…”