Tetrafluorobenzyl norcantharidin carboxylate and synthesis method thereof

Abstract

The invention discloses tetrafluorobenzyl norcantharidin carboxylate and a synthesis method thereof. The structural formula is shown as a formula I, the specific structure of tetrafluorobenzyl norcantharidin carboxylate shown in a formula I is shown in the specification and the synthesis method comprises the following steps that side-chain tetrafluorobenzyl alcohol (compound 5) and norcantharidin(compound 4) undergo a reaction in an organic solvent at a certain temperature under the action of an organic alkali to obtain tetrafluorobenzyl norcantharidin carboxylate shown as a formula I. The synthesis route is shown as follows that: carboxyl is introduced into the molecular structure of the compound disclosed by the invention, so that the water solubility and stability are improved, and dueto the introduction of a fluorine-containing group, the physical property, the chemical property and the biological activity of parent molecules can be remarkably changed, so that the pharmacokineticefficacy can be enhanced. In addition, the raw materials of the synthesis method are easy to obtain, and operation and implementation are very easy.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a class of norcantharidin carboxylic acid tetrafluorobenzyl ester and a synthesis method thereof. Background technique [0002] Cantharidin (CA) is an anti-cancer substance extracted from the insect cantharidin of the genus melaninaceae. It has a good curative effect on liver cancer, ovarian cancer, esophageal cancer, etc. It has a special inhibitory effect on primary liver cancer. However, due to the severe toxicity of cantharidin, it severely stimulates the human urinary system and digestive system, and has certain limitations in its clinical application. The synthetic cantharidin derivative Norcantharidin (Norcantharidin, NCTD) has the same configuration as cantharidin, but the 2, 3 methyl groups are replaced by hydrogen, and the side effects are significantly reduced. Not only can it stimulate the bone marrow and increase white blood cells At the same time, it has the...

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Problems solved by technology

[0005] At present, there are few studies on the introduction of fluorine-containing groups into cantharidin. At the same time, in order to find anti-tumor drug candidates with better efficacy and less toxicity, and to expand the types of cantharidin anti-tumor drugs, we designed a fluorine-containing group The fluorine-containing derivatives of norcantharidin were synthesized, which laid the foundation for the subsequent screening of anticancer activity

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