Aromatic substitution spiro indolyl diketopiperazine compound and synthesis method thereof

A technology for indole diketopiperazines and synthesis methods, which is applied in the field of spiro indole diketopiperazines substituted by aromatic rings and their synthesis, and can solve the problems of poor stereoselectivity, low yield, cumbersome post-treatment, etc. , to achieve the effect of reducing reaction steps, saving costs and improving final yield

Active Publication Date: 2017-03-08
SHAANXI UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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, p

Method used

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  • Aromatic substitution spiro indolyl diketopiperazine compound and synthesis method thereof
  • Aromatic substitution spiro indolyl diketopiperazine compound and synthesis method thereof
  • Aromatic substitution spiro indolyl diketopiperazine compound and synthesis method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] 1) Add 50ml of absolute ethanol as a solvent to a 100ml single-necked flask equipped with a condensation reflux device, then add 34mmol of isatin and 40mmol of hydrazine hydrate to reflux for 3h, cool to 0°C, add 102mmol of sodium hydroxide, reflux for 0.5h, and wait for cooling After reaching room temperature, add 100ml of water, adjust the Ph to 2 with 2mol / L hydrochloric acid, combine the organic phases after liquid separation and extraction, concentrate under reduced pressure and directly have a pink solid precipitate out, and obtain a white solid dihydrogen after recrystallization from absolute ethanol Indole-2-one.

[0042] 2) Add 15ml of absolute ethanol as a solvent in a 50ml single-necked flask equipped with a condensation reflux device, then add 10mmol indolin-2 ketone, 12mmol benzaldehyde and 1mmol piperidine, reflux, TLC detects the progress of the reaction, when the reaction When carried out to 8h, TLC detects that the raw material point of indolin-2 ketone...

Embodiment 2

[0051] 1) Add 50ml of absolute ethanol as a solvent to a 100ml single-necked flask equipped with a condensation reflux device, then add 34mmol of isatin and 40mmol of hydrazine hydrate to reflux for 3h, cool to 0°C, add 102mmol of sodium hydroxide, reflux for 0.5h, and wait for cooling After reaching room temperature, add 100ml of water, adjust the Ph to 2 with 2mol / L hydrochloric acid, combine the organic phases after liquid separation and extraction, concentrate under reduced pressure and directly have a pink solid precipitate out, and obtain a white solid dihydrogen after recrystallization from absolute ethanol Indole-2-one.

[0052] 2) Add 15ml of absolute ethanol as solvent in a 50ml single-necked flask equipped with a condensation reflux device, then add 10mmol indolin-2 ketone, 10mmol benzaldehyde and 1mmol piperidine, reflux, TLC detects the progress of the reaction, when the reaction When carried out to 8h, TLC detects that the raw material point of indolin-2 ketone d...

Embodiment 3

[0061] 1) Add 50ml of absolute ethanol as a solvent to a 100ml single-necked flask equipped with a condensation reflux device, then add 34mmol of isatin and 40mmol of hydrazine hydrate to reflux for 3h, cool to 0°C, add 102mmol of sodium hydroxide, reflux for 0.5h, and wait for cooling After reaching room temperature, add 100ml of water, adjust the Ph to 2 with 2mol / L hydrochloric acid, combine the organic phases after liquid separation and extraction, concentrate under reduced pressure and directly have a pink solid precipitate out, and obtain a white solid dihydrogen after recrystallization from absolute ethanol Indole-2-one.

[0062] 2) Add 15ml of absolute ethanol as a solvent in a 50ml single-necked flask equipped with a condensing reflux device, then add 10mmol indolin-2 ketone, 11mmol benzaldehyde and 1mmol piperidine, reflux, TLC detects the progress of the reaction, when the reaction When carried out to 8h, TLC detects that the raw material point of indolin-2 ketone d...

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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...

Claims

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Application Information

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IPC IPC(8): C07D487/22
CPCY02P20/55C07D487/22
Inventor 马养民范超程佩刘佳苗智乔珂李梦云石磊磊
Owner SHAANXI UNIV OF SCI & TECH
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