Preparation method of anticancer drug lanosterol derivative

A technology for lanosterol and derivatives, which is applied in the field of synthesis of novel lanosterol derivatives, can solve problems such as unfavorable industrial production, long reaction time, and small amount of synthesis, and achieves improved synthesis efficiency, short synthesis steps and simple operation. Effect

Inactive Publication Date: 2018-12-04
INST OF DONGGUAN SUN YAT SEN UNIV +1
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0006] This method also uses lanosterol as a raw material to obtain LD through upprotection, dihydroxylation, oxidation, epoxidation, acylation, and deprotection. However, the reaction time of this system

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  • Preparation method of anticancer drug lanosterol derivative
  • Preparation method of anticancer drug lanosterol derivative
  • Preparation method of anticancer drug lanosterol derivative

Examples

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Embodiment 1

[0043] Example 1: Preparation of lanosterol derivative LD

[0044] a. Preparation of LD-a:

[0045] (1) Add 300.00g (0.7mol) lanosterol, 203.40g (1.9mol) 2,6-lutidine, and 3000ml dichloromethane into a 5000ml reaction flask, stir to dissolve. 371.70 g (1.4 mol) of TBSOTf was added dropwise to the reaction solution at a temperature of 20° C. to 30° C., exothermic during the dropping process, and the rate of addition was controlled so that the reaction temperature did not exceed 40° C. After the dropwise addition, react at 30-40°C for 2-3 hours, take a sample, and monitor the reaction by HPLC. If the area normalization method shows that lanosterol is less than 0.5%, it is judged that the end of the reaction has been reached. Add 1200ml saturated ammonium chloride solution, after stirring for 10min, let stand to separate layers, and collect the organic phase. The aqueous phase was extracted twice with dichloromethane (500 ml each time), and the aqueous phase was discarded. The...

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Abstract

The invention belongs to the technical field of drug synthesis, and relates to a preparation method of a novel anticancer drug lanosterol derivative. According to the method, an intermediate LD-a is generated by taking lanosterol as a starting raw material under the protection of tert-butyl dimethyl silicon (TBS); a Sharpless asymmetric dihydroxylation reaction is carried out on the intermediate LD-a under the action of osmium tetroxide (OsO4), and a vicinal diol compound LD-b is generated; Swern oxidation is carried out on the LD-b compound under the a triethylamine alkaline condition, and aalpha-hydroxy-ketone compound LD-c is generated; an acylation reaction is carried out on the LD-c with acetic anhydride, and an intermediate LD-d is obtained; the intermediate LD-d is subjected to TBSremoval protection, and an intermediate LD-e is obtained; and finally, the target lanosterol derivative LD is obtained through epoxidation. According to the invention, the reaction conditions of allthe steps are relatively mild, the synthetic steps are short, the use of highly toxic or expensive reagents is avoided, the prepared product is high in purity, and the preparation method can be applied to industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and relates to a method for synthesizing novel lanosterol derivatives that can be used for treating cancer. technical background [0002] The study found that lanosterol may be able to prevent the aggregation of proteins that lead to cataracts. In experiments, lanosterol was used to treat the lens of dogs, rabbits, and humans. It was found that the turbidity of the lens and the volume of cataracts were reduced, the symptoms were relieved, and the vision became clearer. Eye drops containing lanosterol have been shown to be an effective treatment for cataracts. This research result has brought good news to those cataract patients who cannot take surgery. Lanosterol can be prepared from chain-like squalene ring closure, and a large amount of lanosterol needs to be extracted from the unsaponifiable matter in lanolin. Due to the special skeleton structure of lanosterol tetracyclic triterpenes, it is o...

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Application Information

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IPC IPC(8): C07J71/00A61P35/00
CPCC07J71/0015A61K31/58A61K31/695A61P35/00C07J71/00C07J75/00
Inventor 谢伟东
Owner INST OF DONGGUAN SUN YAT SEN UNIV
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