Synthetic method of Fuan mycin skeleton

Abstract

The invention discloses a synthetic method of a Fuan mycin skeleton. The method adopts a compound of a formula 1 as a starting material, and a compound of a formula 3 is obtained by removing a silicon protection group in a two-step conversion manner by virtue of Sonogashira coupling reaction. The compound of formula 4 is also used as a starting raw material to obtain the compound of formula 6 by virtue of pinic oxidization and methyl esterification. The compound of formula 3 and the compound of formula 6 have the Sonogashira coupling reaction, a phenolic hydroxyl group is protected by a silicon group, methoxyl is selectively removed, an acetylenic bond is reduced, 6pai electrocyclization is carried out, the phenolic hydroxyl group is activated to have the secondary Sonogashira coupling reaction, the silicon-group protective group is removed, a Ullmann reaction is carried out, methyl protection, pinic oxidization and Fourier-krafz acylation are carried out, esters are hydrolyzed and condensated with amino acid, the acetylenic bond is hydrolyzed into ketone under the gold catalysis, thus obtaining Fuan mycin skeleton protected by pentamethoxyl, and synthesizing the Fuan mycin skeleton. The synthetic route is reasonable in design, raw materials are cheap and easy to get, the operation is simple and easy, a key reaction midbody is easy to modify, and the synthetic research of various polycyclic xanthenone natural products can be realized by utilizing the method.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a synthesis method for synthesizing fuanmycin skeleton. Background technique [0002] Fuanmycin is a type of polycyclic structure belonging to xanthone natural products. The fuanmycin backbone isolated from marine Streptomyces exhibited good cytotoxicity against colon and gastric cancer cells, with an IC 50 The value reaches 0.8 μM (Dong-Chan Oh et.al., J.Nat.Prod., 2015, 78, 524–529). The structure of the natural product of fuanmycin mainly includes a xanthone ring and a chiral amino acid fragment, so the difficulty in synthesizing this natural product also lies in the construction of xanthanone and the introduction of chiral amino acids. Its structure is as follows: [0003] [0004] At present, there is no report on the total synthesis of fuanmycin natural products. And as a natural product with a similar structure to fuanmycin 1 、A 2 , is a polycyclic natural product...

AI Technical Summary

Problems solved by technology

[0016] (1) The reagents used in the reaction involve toxic, harmful and dangerous reagents, and the reaction steps are not easy to operate and not easy to scale up

[0017] (2) The synthesis efficiency is low, especially the reaction yield of the 6π electric ring is very low, which is not conducive to the large-scale preparation of the reaction

[0018] (3) What is synthesized is a racemic natural product, which is not conducive to further research on its medicinal chemistry

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