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2, 4-pyrrolidine-diketone compounds and synthesis method thereof

A compound and diketone technology, applied in the field of new compounds and their synthesis, can solve the problems of poor stereoselectivity, long route, low total yield, etc., and achieve the effects of good biological activity, short route and high yield

Inactive Publication Date: 2014-01-01
EAST CHINA NORMAL UNIV
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  • Abstract
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  • Application Information

AI Technical Summary

Problems solved by technology

[0007] 2) Total synthesis by Rodríguez group; in 2000, Rodríguez group reported the second synthetic route of (-)-equisetin (1), with a total of 13 steps and a total yield of 10.1%, which has greatly improved the synthesis , but the route is still longer
[0013] In summary, although there are several routes for synthesizing (-)-equisetin (1), each route has problems such as long route, low overall yield, and poor stereoselectivity. Therefore, it is necessary to develop an efficient synthetic route, and a series of (-)-equisetin (1)-like compounds are synthesized through this route, and it is still of high research significance to find compounds with better activity and lower toxicity

Method used

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  • 2, 4-pyrrolidine-diketone compounds and synthesis method thereof
  • 2, 4-pyrrolidine-diketone compounds and synthesis method thereof
  • 2, 4-pyrrolidine-diketone compounds and synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Synthesis of compound 5

[0048]

[0049] Synthesis of compound 11: Weigh 10 (3.4g, 8.70mmol) in a 200mL dry reaction flask, add 44mL (0.2M) of tetrahydrofuran, add n-butyllithium (6mL, 9.6mmol) dropwise at -78°C, and After reacting at ℃ for 10 min, add 9 (872 mg, 2.90 mmol) in 5 mL THF at -78 °C, react at this temperature for 30 min, then raise to 0 °C and react for 10 min. After the reaction was complete, 20 mL of saturated ammonium chloride solution was added thereto, stirred at room temperature for 10 min, the tetrahydrofuran was spin-dried, extracted with (50 mL×2) ethyl acetate, the organic phases were combined and washed with saturated ammonium chloride (20 mL×2) The solution was washed with saturated sodium chloride (20mL×1), dried over anhydrous sodium sulfate, and spin-dried. Flash column chromatography (1% ethyl acetate / petroleum ether) yielded 812 mg of yellow liquid, and the yield was 83%. HRMS(EI):Exact mass calcd for C 20 h 32 SO 2 [M] + :336.212...

Embodiment 2

[0057] Synthesis of compound 6

[0058]

[0059] Synthesis of compound 16: Weigh 15 (147mg, 0.41mmol) in a 50mL reaction flask, add 20mL (0.02M) of tetrahydrofuran and 13 (105mg, 0.82mmol), triethylamine (228μL, 1.64mmol) and incubate at 0°C Quickly added silver trifluoroacetate (142mg, 0.62mmol), reacted at this temperature for 10min. After the reaction was complete, 0.5 mL of saturated sodium chloride solution was added thereto, stirred at room temperature for 5 min, and passed over diatomaceous earth. Purified by column chromatography (30% ethyl acetate / petroleum ether) to obtain 150 mg of an orange solid with a yield of 90%. HRMS(EI):Exact mass calcd for C 24 h 35 NO 4 [M] + :401.2566;Found:401.2567, 1 H NMR (400MHz, CDCl 3)δ5.47–5.27(m,3H),5.26–5.11(m,1H),4.52(dd,J=8.3,3.6Hz,1H),3.77–3.55(m,3H),3.49(t,J= 6.4Hz, 2H), 3.31(d, J=15.8Hz, 1H), 2.54(dd, J=9.1, 4.8Hz, 1H), 2.36(d, J=7.8Hz, 2H), 2.27–2.09(m, 3H),2.09–1.83(m,3H),1.84–1.62(m,3H),1.59(dd,J=8.7,3.6Hz,2H),...

Embodiment 3

[0063] Synthesis of compound 7

[0064]

[0065] Synthesis of compound 18: Weigh 15 (60mg, 0.17mmol) in a 20mL dry reaction tube, add 4mL (0.1M) of tetrahydrofuran and 17 (35mg, 0.24mmol), triethylamine (100μL, 0.68mmol) and dissolve in 0 Silver trifluoroacetate (70 mg, 0.26 mmol) was added quickly at ℃, and reacted at this temperature for 10 min. After the reaction was complete, 0.5 mL of saturated sodium chloride solution was added thereto, stirred at room temperature for 5 min, and passed over diatomaceous earth. Purified by column chromatography (5% ethyl acetate / petroleum ether) to obtain 52 mg of white solid. 75% yield. HRMS(EI):Exact mass calcd for C 25 h 39 NO 4 [M] + :417.2879;Found:417.2877, 1 H NMR (400MHz, CDCl 3 ) 1 H NMR (400MHz, CDCl 3 )δ5.48–5.28(m,3H),5.19(dd,J=15.5,7.6Hz,1H),4.92(t,J=8.8Hz,1H),3.87–3.56(m,4H),3.53–3.30 (m,1H),3.02–2.71(m,3H),2.54(dd,J=8.7,4.7Hz,1H),2.28–2.07(m,1H),1.70(ddd,J=22.5,18.8,9.6Hz ,6H),1.60–1.53(m,3H),1.52–1.37(m,1H),...

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Abstract

The invention discloses equisetin-derived 2, 4-pyrrolidine-diketone compounds. The diketone compounds have the structure shown in the specification, wherein R1 is hydrogen, alkyl, aryl or a heteroatom group containing O and N; R2 is hydrogen or alkyl; R3 is hydrogen or alkyl. A synthesis method of the diketone compounds comprises eight steps, wherein aldehyde II is prepared in the four steps; a polyene compound III is prepared through a Wittig reaction or Horner-Wadswort-Emmons reaction; a compound IV' is prepared through a Diels-Alder reaction; finally a compound V is prepared by ammonolysis and Dieckmann condensation. The compounds have relatively high biological activity and bring the foundation to the research and development of anti-cancer medicaments; the raw materials used in synthesis are simple and easy to obtain; the synthesis process is simple to carry out; the yield is relatively high.

Description

technical field [0001] The present invention relates to new compounds and their synthesis methods, especially a class of novel organic compounds based on the equisetin structure and their synthesis routes. Background technique [0002] Tetramic acid is a compound containing a typical 2,4-pyrrolidine-dione structural unit in its skeleton. Representative compounds of such natural products include (-)-equisetin (1), fusarisetin A (2), diaporthichalasin ( 3), (-)-tirandamycin (4), etc. The compound containing this unit has a wide range of biological activities, and its anti-tumor property is particularly outstanding, so it has good potential medicinal value. Since the 1960s, Tetramic acid-like natural products have gradually attracted the attention of synthetic chemists, and certain progress has been made in their configuration and synthesis, laying the foundation for subsequent development. [0003] [0004] In 1974, Fusarium (-)-equisetin (1) was isolated for the first ti...

Claims

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Application Information

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IPC IPC(8): C07D487/04C07D207/40
CPCC07D487/04C07D207/36
Inventor 孔丽丽尹军高栓虎
Owner EAST CHINA NORMAL UNIV
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