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Method for preparing compound pyrrolo [2, 1-a] isoquinoline alkaloid with lamelline structure by one-pot method

A technology for compounds and alkaloids, applied in the field of drug synthesis, can solve the problems of limited types of compounds and low functional group tolerance, and achieve the effects of effective cytotoxic activity, simple method and simple reaction conditions

Inactive Publication Date: 2021-09-17
CHANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these methods usually have one or more of the following defects, the need to use peroxide or oxygen, the tolerance of functional groups is not high, and the types of synthetic compounds are limited

Method used

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  • Method for preparing compound pyrrolo [2, 1-a] isoquinoline alkaloid with lamelline structure by one-pot method
  • Method for preparing compound pyrrolo [2, 1-a] isoquinoline alkaloid with lamelline structure by one-pot method
  • Method for preparing compound pyrrolo [2, 1-a] isoquinoline alkaloid with lamelline structure by one-pot method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add compound (Z)-2-methyl-5-phenylpent-2-en-4-yne aldehyde (0.5 mmol) and 1,2,3,4-tetrahydroisoquinoline ( 1 mmol), trifluoroacetic acid (1 mmol) and toluene (2 mL). The reaction was heated to 130° C. on an oil bath, and reacted for 5 hours. After the completion of the reaction was monitored by TLC spotting, the reaction solution was concentrated, and a yellow liquid 5a was obtained by flash column chromatography (petroleum ether and ethyl acetate as eluents), with a yield of 88%. 1 H NMR (400MHz, CDCl 3 )δ7.56(d, J=7.1Hz, 2H), 7.41(t, J=7.7Hz, 3H), 7.32(t, J=7.3Hz, 1H), 7.23(d, J=7.3Hz, 1H) ,7.08(tdd,J=15.1,10.7,4.2Hz,2H),6.77(d,J=1.5Hz,1H),6.30(s,1H),4.11(t,J=6.4Hz,2H),3.14( t,J=6.4Hz,2H).

Embodiment 2

[0033] Add compound (Z)-2-methyl-5-phenylpent-2-en-4-yneal (0.5 mmol) and 6-chloro-1,2,3,4-tetrahydro to a 25 mL Shrek tube Isoquinoline (1 mmol), trifluoroacetic acid (1 mmol) and toluene (2 mL). The reaction was heated to 130° C. on an oil bath, and reacted for 5 hours. After the completion of the reaction was monitored by TLC spotting, the reaction solution was concentrated, and a light green solid 5b was obtained by flash column chromatography (petroleum ether and ethyl acetate as eluents), with a yield of 65%. mp:147-148℃. 1 H NMR (400MHz, CDCl 3)δ7.52–7.47(m,2H),7.40(t,J=7.5Hz,2H),7.34–7.27(m,2H),7.21(d,J=2.0Hz,1H),6.99(dd,J =8.5,2.2Hz,1H),6.76(d,J=2.6Hz,1H),6.27(d,J=2.6Hz,1H),4.08(t,J=6.4Hz,2H),3.10(t,J =6.4Hz,2H).

Embodiment 3

[0035] Add compound (Z)-2-methyl-5-phenylpent-2-en-4-yneal (0.5 mmol) and 5-chloro-1,2,3,4-tetrahydro to a 25 mL Shrek tube Isoquinoline (1 mmol), trifluoroacetic acid (1 mmol) and toluene (2 mL). The reaction was heated to 130° C. on an oil bath, and reacted for 5 hours. After the completion of the reaction was monitored by TLC spotting, the reaction solution was concentrated, and a yellow solid 5c was obtained by flash column chromatography (petroleum ether and ethyl acetate as eluents), with a yield of 49%. mp:92-93℃. 1 H NMR (400MHz, CDCl 3 )δ7.48(d, J=7.3Hz, 2H), 7.39(t, J=7.4Hz, 2H), 7.32(d, J=7.2Hz, 1H), 7.26(s, 1H), 7.14(d, J=7.9Hz, 1H), 6.94(t, J=7.9Hz, 1H), 6.77(s, 1H), 6.28(s, 1H), 4.10(t, J=6.4Hz, 2H), 3.28(t, J=6.3Hz, 2H).

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Abstract

The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for preparing a compound pyrrolo [2, 1-a] isoquinoline alkaloid with a lamelline structure through a one-pot method. According to the invention, a tetrahydroisoquinoline derivative and a (Z)-5-phenylpent-2-ene-4-alkyne aldehyde derivative are used as raw materials, are heated to 100-130 DEG C under the catalysis of trifluoroacetic acid, and reacted for 5 hours, so that the 1-phenyl-5, 6-dihydropyrrolo [2, 1-a] isoquinoline alkaloid is obtained by a one-step method. The method has the advantages that the reaction condition is simple, the substrate has high universality and can be well converted into the target compound, an oxidizing agent does not need to be additionally used, and the compound needs to be stored in a dark place under the condition of deuterated chloroform. The compounds provide a relatively simple method for synthesizing medicines for treating sterility, and the skeleton has effective cytotoxic activity on in-vitro tumor cells.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a method for preparing pyrrolo[2,1-a]isoquinoline alkaloids, a compound of fispirin structure, in one pot. Background technique [0002] Pyrrolo[2,1-a]isoquinoline alkaloids are the core skeleton of marine polycyclic spirulina alkaloids, a class of nitrogen-bridged heterocyclic molecules with unique biological activities[1.Fan,H.; Peng , J.; Hamann, M.T.; Hu, J.-F. Chem. Rev. 2008, 108, 264-287.2. Fukuda, T.; Ishibashi, F.; Iwao, M. Heterocycles 2011, 83, 491-529.]. Picospirin D (structure shown in the following formula) is the most active of the Pispirulin series compounds, can inhibit topoisomerase I, has strong cytotoxicity to a series of cancer cells, affects the cell cycle, and guides apoptosis Death. [(a) Marco, E.; Laine, W.; Tardy, C.; Lansiaux, A.; 3796-3807. (c) Aubry, A.; Pan, X.-S.; Fisher, L.M.; Jarlier, V.; Cambau, E. Antimicrob. Agents Che...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 李剑侯国权高旭刘莉
Owner CHANGZHOU UNIV
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