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Chiral indolopyrrole alkaloid and preparation method thereof

A technology for indolopyrrole and alkaloids, which is applied in the field of chiral indolopyrrole alkaloids and their preparation, can solve problems such as difficult multi-functional groups and limited substrate range diversity, and achieve good enantioselectivity, The effect of enriching drug molecule library and simple reaction conditions

Inactive Publication Date: 2021-11-19
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When constructing alkaloids containing 3α-amino-hexahydropyrrole[2,3-b]indole structure, the nucleophilicity at the C-3 position of the indole ring is often used. On the basis of the existing indole ring It is functionalized, and the construction of the azaquaternary carbon center is realized through the electrophilic-cyclization process, which limits the diversity of the substrate range, and it is difficult to synthesize a multifunctional indole skeleton (Angew.Chem., Int. Ed.2011,50,2716; Angew.Chem.,Int.Ed.2014,53,5600)

Method used

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  • Chiral indolopyrrole alkaloid and preparation method thereof
  • Chiral indolopyrrole alkaloid and preparation method thereof
  • Chiral indolopyrrole alkaloid and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0033] Preparation of Compound 1

[0034]

[0035] Add 0.10mmol of diphenylamine S1-1, 0.11mmol of pyrazolone ketimine S2, 0.001mmol of chiral phosphoric acid catalyst CPA I, 50mg of molecular sieves, and 1.0mL of chloroform into the reaction flask, and react at 0°C for 12h. Column separation gave white solid 1 with a yield of 92%.

Embodiment 2

[0037] Preparation of compound 2

[0038]

[0039] Add 0.10mmol 4-phenyldiphenylamine S1-2, 0.11mmol pyrazolone imine S2, 0.001mmol chiral phosphoric acid catalyst CPA I, 50mg molecular sieves, and 1.0mL chloroform into the reaction flask, react at 0°C for 12h, and the reaction is complete Afterwards, a yellow solid 2 was obtained by separation on a silica gel column with a yield of 90%.

[0040] Compound 3-15 was prepared from the corresponding aniline and pyrazolone imine according to the above method.

Embodiment 3

[0042] Preparation of compound 16

[0043]

[0044] Add 0.10mmol nitrogen phenyl 2-naphthylamine S1-16, 0.11mmol pyrazolone imine S2, 0.001mmol chiral phosphoric acid catalyst CPA II, 1.0mL DCM into the reaction flask, react at -20°C for 12h, and the reaction is complete Afterwards, a white solid 16 was obtained by separation on a silica gel column with a yield of 98%.

[0045] Compounds 17-25 were prepared from the corresponding naphthylamine and pyrazolone imine according to the above method.

[0046] min. 1 H NMR (500MHz, acetone-d 6 ):δ8.02(d,J=10.0Hz,2H)7.58(d,J=10.0Hz,2H),7.49-7.45(m,3H),7.39-7.30(m,3H),7.21(s,1H ),7.13-7.07(m,2H),6.75(t,J=10.0Hz,1H),6.44(d,J=10.0Hz,1H),5.70(s,1H),1.43(s,9H),1.40 (s,3H). 13 C NMR (126MHz, DMSO-d 6 ):δ169.43,157.17,148.62,140.76,140.49,130.81,130.00,129.40,128.09,127.09,125.96,124.65,124.54,119.30,118.71,108.05,89.52,80.61,72.55,28.41,17.63.HRMS(ESI):m / z calculated for C 27 h 28 N 4 o 3 [M+H + ]457.2234, found 457.2233. ...

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Abstract

The invention relates to a chiral indolopyrrole alkaloid and a preparation method thereof. The preparation method comprises the steps: dissolving pyrazolone imine and an aromatic amine derivative in a solvent, and carrying out a 3+2 series cyclization reaction under the action of a chiral phosphoric acid catalyst to prepare the chiral indolopyrrole alkaloid. Compared with the prior art, the method has the advantages that the use of a metal catalyst is avoided, the synthesis of the chiral indolopyrrole alkaloid can be realized in a high-yield and high-enantioselectivity manner, a possible potential strategy is provided for tumor treatment, and the method has a relatively good application prospect and a certain practical application value.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, and in particular relates to a chiral indolopyrrole alkaloid and a preparation method thereof. Background technique [0002] Indolopyrrole alkaloids have attracted much attention in the fields of medicinal chemistry and organic chemistry. Among them, indolopyrrole compounds with different types of substituents at the C-3 position of indole have been studied most extensively on their chemical structures and biological activities. The pharmacological effects of many compounds are well understood and exploited, including muscle relaxants, potassium channel blockers, and anticancer activity. [0003] Among the structure types of many indole alkaloids, the alkaloids containing 3α-amino-hexahydropyrrole [2,3-b]indole structure are one of the most important ones. Due to the existence of two adjacent chiral centers at the C-3 azaquaternary carbon and the C-2 position in the molecular structure...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 丁同梅王冠军张书宇
Owner SHANGHAI JIAO TONG UNIV
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