A kind of aromatic ring substituted spiro ring indole diketopiperazine compound and its synthetic method

Abstract

The invention discloses an aromatic substitution spiro indolyl diketopiperazine compound and a synthesis method thereof. Glycine is used as a raw material and subjected to esterification reaction with methyl alcohol and thionyl chloride to obtain methyl glycinate hydrochloride, methyl glycinate hydrochloride and aromatic aldehyde are subjected to condensation reaction to obtain Schiff base, isatin is used as a raw material and subjected to reduction reaction under the action of hydrazine hydrate to obtain indoline-2-ketone, indoline-2-ketone and benzaldehyde are subjected to Knoevenagel reaction under piperidine catalysis to obtain 3-phenylidene-1,3-dihydro-2H-indol-2 ketone, 3-phenylidene-1,3-dihydro-2H-indol-2 ketone and Schiff base are subjected to 1,3-dipole cycloaddition reaction under catalysis of chiral ligand (S)-TF-BiphamPhos / AgoAc to obtain spiro pyrrolidine, and protecting group removal and ring closure are carried out on spiro pyrrolidine and N-(9-fluorene methoxycarbonyl)-L-prolyl chloride through base catalysis to obtain the target product. The method has the advantages of being simple in path, high in yield, high in diastereoselectivity and single in product spatial configuration, and the raw materials are low in price and easy to obtain.

Description

technical field [0001] The invention relates to the field of synthesis of natural alkaloids, in particular to a spiro-ring indole diketopiperazine compound substituted by an aromatic ring and a synthesis method thereof. Background technique [0002] Aryl ring-substituted spirotryprostatins (spirocyclic indole diketopiperazines) are a special class of alkaloids with a five-ring structure, including multiple chiral centers. The spiro indole structure and diketopiperazine structure in Spirotryprostatins are the key structures of many synthetic and natural medicines. Compounds with these two structures have good biological activities. For example, compounds containing spiro indole structures have antitumor properties. , antibacterial, anti-HIV and antimalarial and other biological activities; compounds containing diketopiperazine structures have biological activities such as cytotoxicity, antibacterial, antifungal, and anti-blockage. Spirotryprostatins alkaloids substituted by a...

AI Technical Summary

Problems solved by technology

At present, methods for synthesizing aromatic ring-substituted spirotryprostatins alkaloids mainly include methods such as oxidative rearrangement, [3+2] cycloaddition reaction, palladium catalysis, and free radical addition. These methods have poor stereoselectivity, complex reaction routes, and low yield. Low, cumbersome post-processing and other defects

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