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A kind of spirocyclic indole diketopiperazine alkaloid and its synthesis method and application

A technology of indole diketopiperazine and synthesis method, which is applied in the direction of bulk chemical production, organic chemistry, antibacterial drugs, etc., can solve the problems of complex reaction route, cumbersome post-processing, high cost, etc., and achieve the purpose of improving reaction yield, The effect of convenient processing and reduced dosage

Active Publication Date: 2015-11-18
SHAANXI UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, the synthesis of such alkaloids mainly adopts methods such as free radical addition to form a ring, metal complexes participating in [5+2] cycloaddition, and 1,3-dipolar cycloaddition. Although these methods have successfully constructed Spiral ring structure and the connection of indole and diketopiperazine units, but most of the methods have defects such as high cost, complicated reaction route, low yield, and cumbersome post-treatment

Method used

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  • A kind of spirocyclic indole diketopiperazine alkaloid and its synthesis method and application
  • A kind of spirocyclic indole diketopiperazine alkaloid and its synthesis method and application
  • A kind of spirocyclic indole diketopiperazine alkaloid and its synthesis method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] 1) Add 50mL of isopropanol to a 100mL three-necked flask equipped with a stirrer, a constant pressure dropping funnel, and a condensing reflux device, and then add 12mmol of propionaldehyde into the three-necked flask under stirring, and after mixing evenly, add 10mmol of L-tryptophan methyl ester hydrochloride, then heated to reflux state reaction, carried out with TLC monitoring reaction in the reflux reaction process, reacted 4h, now TLC detects that L-tryptophan methyl ester hydrochloride raw material point disappears and Generate two new product points, end the reaction, evaporate isopropanol and excess propionaldehyde under reduced pressure to obtain solid A, solid A is rinsed with toluene to remove soluble impurities, and then dried to obtain mixed enantiomeric hydrochloride (a cis-trans mixture of mix-2a-HCl); wherein, the TLC developer is a mixture of ethyl acetate and methanol at a volume ratio of 10:1;

[0034] 2) Mix nitromethane and toluene uniformly at a v...

Embodiment 2

[0049] 1) Add about 50mL of isopropanol into a 100mL three-necked flask equipped with a stirrer, a constant pressure dropping funnel, and a condensing reflux device, then add 12mmol of n-butyraldehyde into the three-necked flask under stirring, stir and mix evenly, and then add 10mmol of L-tryptophan methyl ester hydrochloride, then heated to the reflux state to react, during the reflux reaction, use TLC to monitor the reaction, react for 4h, at this time TLC detects the raw material point of L-tryptophan methyl ester hydrochloride Disappear and generate two new product points, end the reaction, evaporate isopropanol and excess n-butyraldehyde under reduced pressure to obtain solid A, solid A is rinsed with toluene to remove soluble impurities, then dried to obtain mixed enantiomers Hydrochloride (mix-2b-HCl cis-trans mixture).

[0050] 2) Mix nitromethane and toluene uniformly at a volume ratio of 1:1 to obtain an inducer for crystallization-induced asymmetric transformation;...

Embodiment 3

[0065] 1) Add 50mL of isopropanol to a 100mL three-necked flask equipped with a stirrer, a constant pressure dropping funnel, and a condensing reflux device, and then add 12mmol of n-valeraldehyde to the three-necked flask while stirring, and after mixing evenly, add 10mmol of L-tryptophan methyl ester hydrochloride, then heated to reflux state reaction, carried out with TLC monitoring reaction in the reflux reaction process, reacted 4h, now TLC detects that L-tryptophan methyl ester hydrochloride raw material point disappears and Generate two new product points, end the reaction, evaporate isopropanol and excess n-valeraldehyde under reduced pressure to obtain solid A, solid A is rinsed with toluene to remove soluble impurities, and then dried to obtain mixed enantiomeric hydrochloric acid Salt (a cis-trans mixture of mix-2c-HCl); wherein, the TLC developer is a mixture of ethyl acetate and methanol at a volume ratio of 10:1;

[0066]2) Mix nitromethane and toluene uniformly ...

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Abstract

The invention relates to spiro indole diketopiperazine alkaloid, and a synthesis method and an application of the spiro indole diketopiperazine alkaloid. The synthesis method comprises the steps that L-tryptophan methyl ester hydrochloride and fatty aldehyde perform Pictet-Spengler reaction to form enantiomeric hydrochloride, an inducer for inducing asymmetric conversion through crystallization induces the asymmetric conversion to form a single-configuration product, the single-configuration product performs Schotten-Baumann reaction to form an amido bond, then a spiral structure is obtained by NBS (N-bromosuccinimide) rearrangement, a protecting group is removed from the spiral structure under base catalysis, and the spiral structure is subjected to ring closing to form the spiro indole diketopiperazine alkaloid. The method has the advantages that the method is low in cost, simple and convenient in path, high in yield and easy to process, an end product and a natural product are the same in configuration, etc. The prepared spiro indole diketopiperazine alkaloid can be further applied to preparation of antibiotics.

Description

technical field [0001] The invention relates to the field of total synthesis of natural alkaloids, in particular to a spirocyclic indole diketopiperazine alkaloid and its synthesis method and application. Background technique [0002] Spiral indole diketopiperazine alkaloids, as a kind of indole alkaloids with special structure, are widely distributed in nature, especially in the form of fungal secondary metabolites. Studies have found that this type of alkaloid can inhibit mouse breast cancer cells (tsFT210) in the G2 / M phase, and confirmed its effect on human chronic myelogenous leukemia (K562) cells and human promyelocytic leukemia (HL-60) Cell lines such as cells have cytotoxic activity. It is also reported that some of these compounds also have anti-HIV, antibacterial, insect tremor and other activities. Based on the above characteristics, in recent years, there have been many reports on its synthesis research. At present, the synthesis of such alkaloids mainly adopt...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/22A61P31/04A61P31/10
CPCY02P20/55
Inventor 马养民吴昊任德成张金李延超张弘弛
Owner SHAANXI UNIV OF SCI & TECH
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