Asymmetric cyclobutane derivatives, preparation method and applications thereof

Abstract

The invention discloses asymmetric cyclobutane derivatives (synthetic derivatives G of rabdosia scoparia lactones), which are named as scopariusicide derivatives, a pharmaceutical composition taking the asymmetric cyclobutane derivatives as the active component, a preparation method of asymmetric cyclobutane derivatives, and an application of asymmetric cyclobutane derivatives in preparation of immuno-suppressive drugs. According to the preparation, scopariusicides, which is derived from pharmaceutical plants, is taken as the template; a precursor compound ent-clerodane diterpene A is taken as the initial raw material, a series of artificial analogues are obtained through six steps of chemical synthesis; the basic structure of the derivatives has a characteristic that ent-clerodane hetero-diterpene has an asymmetric cyclobutane segment, the side chain and aromatic ring of the derivatives may have different substituents, and thus there are many kinds of derivatives. The compounds are synthesized for the first time, the synthesis route is novel, and the derivatives have potential bioactivity, can be used as the lead compounds of immuno-suppressive drugs, and have a very important research value and application prospect.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis of natural products, and in particular relates to an asymmetric cyclobutane derivative and a preparation method and application thereof. Background technique [0002] Ciamician first discovered the [2+2] photochemical reaction in 1908, but there are very few successful examples of the [2+2] reaction between heteromolecules, which has always been a difficulty in organic synthesis. This is determined by the characteristics of the molecule itself. First, if one of the molecules in the reaction system is a chain molecule, the energy will basically be spent on the inversion of the double bond configuration, and the [2+2] photochemical reaction will not occur. Second, even if the [2+2] reaction occurs, its products are quite complex. Some brilliant organic chemists have tried to solve the problem of poor stereoselectivity in the synthesis world, and several methods have also been developed, i...

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Problems solved by technology

However, these reactions have disadvantages such as narrow substrate applicability and product immobilization, and are rarely applied to practical synthesis.

In 2005, Daugulis and his collaborators developed a method of using 8-aminoquinoline or o-aminomethyl sulfide as a directing agent to activate the C-H bond at the β-position of the carbonyl group. Afterwards, its methodology was widely studied, but it was applied to Fewer examples of success in total synthesis research

[0003] At present, there is no report in the prior art that combines the intermolecular 2+2 photochemical reaction with hydrocarbon activation to complete the preparation method of symmetrical cyclobutane derivative G

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