Method for synthesizing natural product (+/-)-Pestaloxazine A from ornithine

A synthesis method and compound technology, applied in the direction of silicon organic compounds, chemical instruments and methods, compounds of group 4/14 elements of the periodic table, etc., can solve problems such as limiting pharmacological activity and pharmacokinetics research

Active Publication Date: 2017-12-12
YANGZHOU BLUE BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In the prior art, there is no report on the synthesis method of the natural product (±)-pestaloxazine A, and the amount of the compound obtained simply by natural extraction is small, which greatly limits the research on its pharmacological activity and pharmacokinetics

Method used

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  • Method for synthesizing natural product (+/-)-Pestaloxazine A from ornithine
  • Method for synthesizing natural product (+/-)-Pestaloxazine A from ornithine
  • Method for synthesizing natural product (+/-)-Pestaloxazine A from ornithine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100]

[0101] Weigh formula B compound (R 1 H, 130mg, 1.0mmol) was dissolved in 25mL of dry toluene / acetonitrile (volume ratio 3 / 2) mixture, DCC (1.0mmol) and DMAP (0.2mmol) were added, and after stirring at room temperature for 15 minutes, the formula A was added Compound (25.6 mg, 0.1 mmol), heated to 60 to 65 °C for 24 hours, filtered, concentrated under reduced pressure, and subjected to silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: methanol / dichloromethane =1 / 10), the compound of formula I (44.2 mg) was obtained with a yield of 92%, ESI-MS (m / z): 481.2 [M+H] + .

[0102] Note: The compound of formula A used in this reaction is a racemate, and the compound of formula I obtained is also a racemate.

Embodiment 2

[0104]

[0105] (1) using R 1 Be the formula B compound (1.0mmol) of TBS to replace R in embodiment 1 1 Be the formula B compound of H, according to the operation in embodiment 1 (silica gel column chromatography eluent is changed into sherwood oil / ethyl acetate), can obtain formula II compound (65.9mg, R 1 is TBS), ESI-MS (m / z): 709.4 [M+H] + ;

[0106] (2) Weigh the compound of formula II (50mg, 0.07mmol, R 1 is TBS) was dissolved in 5.0mL THF, added 1.0mLBu 4 NF solution in THF (Bu 4 The concentration of NF is 1.0mol / L), after reacting at room temperature for 0.5-2h, add water (1.0 mL) to stop the reaction, evaporate THF under reduced pressure, extract with EtOAc (20mL), and wash the organic layer with anhydrous Na 2 SO 4 After drying, filtering and concentrating, 30.5 mg of white solid was obtained by recrystallization or silica gel column chromatography, which is the compound of formula I (yield about 90%).

[0107] NOTE: This example uses R 1 For TES, TMS, TBD...

Embodiment 3

[0109]

[0110] (1) Weigh the compound of formula A (25.6 mg, 0.1 mmol) and dissolve it in 5 mL of THF, add 200 μL of triethylamine, compound of formula C (0.25 mmol, X is Cl, R 1 MOM) and a catalytic amount of DMAP, after reacting at room temperature for 2 hours, TLC detected that the reaction raw materials almost completely disappeared, extracted twice with ethyl acetate (25mL), dried the organic layer over anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography (The eluent is EtOAc / petroleum ether=10:1~6:1), to obtain the compound of formula II (48.4 mg, X is Cl, R 1 MOM), yield 85.2%, ESI-MS (m / z): 569.3 [M+H] + ;

[0111] (2) Weigh the compound of formula II (30mg, 0.05mmol, R 1 is MOM) dissolved in 5.0 mL CH 2 Cl 2 , add 60 μL trifluoroacetic acid (TFA), react at room temperature for 4 hours, add saturated NaHCO 3 solution to terminate the reaction with CH 2 Cl 2 (20mL) extraction, organic layer with anhydrous Na 2 SO 4 Afte...

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Abstract

The invention relates to a method for synthesizing a natural product (+ / -)-Pestaloxazine A from ornithine. The method comprises the steps of carrying out series reaction such as condensation, oxidation and cyclization on the protected ornithine to obtain a symmetric dioxazine alkane spiropiperazine compound A; and then carrying out condensation reaction on the symmetric dioxazine alkane spiropiperazine compound A and a side chain compound B to prepare the natural product (+ / -)-pestaloxazine A.

Description

technical field [0001] The invention belongs to the field of total synthesis of natural products, in particular to a method for synthesizing natural product (±)-pestaloxazine A from ornithine. The natural product (±)-pestaloxazine A has a novel structure and significant activity, and has the potential to be developed as a lead compound for anti-EV71 active drugs. Background technique [0002] Enterovirus 71 (EV71) is the main pathogen causing hand, foot and mouth disease, mostly infecting infants and preschool children. Since the Ministry of Health listed hand, foot and mouth disease as a Class C infectious disease in 2008, by the end of 2014, there were 11.89 million patients in China, resulting in 3220 deaths. Recent studies have shown that EV71 has become an important neurotropic virus, which can cause acute flaccid paralysis and encephalitis, leading to cardiopulmonary failure and death. At present, the number of patients and deaths is still increasing year by year, bu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/20C07C271/22C07D241/08C07F7/08C07F7/18
Inventor 于跃
Owner YANGZHOU BLUE BIOMEDICAL TECH CO LTD
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