Preparation method for synthesizing romidepsin dipolymer romipeptide A

A technique for synthesizing romidepsin and romidepsin, which is applied in peptide preparation methods, chemical instruments and methods, organic chemistry, etc., and can solve the problem of low yield

Active Publication Date: 2021-10-26
TAIZHOU VOCATIONAL COLLEGE OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is a dipolymer of romideptide, which has good antitumor activity and has the potential to be further developed as an antitumor drug, but its yield is not high, so it is necessary to develop a new efficient preparation of romideptide A method

Method used

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  • Preparation method for synthesizing romidepsin dipolymer romipeptide A
  • Preparation method for synthesizing romidepsin dipolymer romipeptide A
  • Preparation method for synthesizing romidepsin dipolymer romipeptide A

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1 Compound Synthesis

[0018] 1.0 g of romidepsin raw material was dissolved in 50 mL of acetone, then 1.0 L of NaOH (0.01 M, added dropwise in 20 minutes) was added and the reaction was stirred until the romidepsin reaction was completed and the reaction was terminated.

[0019] The reaction solution was extracted twice with 2L of ethyl acetate to obtain an ethyl acetate phase, which was washed with water until neutral, dried with anhydrous sodium sulfate and concentrated to dryness, and then separated by semi-preparative column chromatography to obtain romidepsin dimerization. compound (compound 1). The semi-preparative column chromatography conditions are as follows:

[0020] The chromatographic column is: Eclipse XDB-C18, 9.4mm×250mm;

[0021] The mobile phase is: methanol: water = 75:25;

[0022] Detection wavelength: 210nm;

[0023] Flow rate: 1.5ml / min;

[0024] Column temperature: room temperature

[0025] Retention time (weight): 13.4 mins (216 mg...

Embodiment 2

[0026] Example 2 Structure identification

[0027] Compound 1 obtained in Example 1, (c 0.07, EtOH), UV(EtOH) λmax nm(logε): 202(3.45).HRESIMS m / z 1081.4221[M+H] + (C 48 H 73 N 8 O 12 S 4 The calculated value is 1081.4231). 1 H and 13 CNMR data and references (Xiong L, Chen Ca, Min TL, Hu HF. Romipeptides A and B, two newromidepsin derivatives isolated from Chromobacterium violaceum No.968 and their antitumor activities in vitro. Chin J Nat Med, 2019, 17(2): 155-160.) The comparison is shown in Table 1. In summary, compound 1 is romipeptide A, and the structure is shown in formula 2.

[0028] Table 1 Nuclear magnetic data (DMSO-d6) of the dimer obtained in Example 1

[0029]

[0030]

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Abstract

The invention relates to a preparation method for synthesizing a romidepsin dipolymer romipeptide A. According to the preparation method, romidepsin is used as a precursor, the romipeptide A is synthesized in one step, the process is simple, and a large amount of romipeptide A can be prepared.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a preparation method for synthesizing romidepsin dimer polymer romipeptide A. Background technique [0002] Romidepsin (romidepsin, structure shown in formula 1), also known as FK228 and FR901228, is an HDAC inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the regulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. In vitro, romidepsin causes accumulation of acetylated histones, and induces cell cycle arrest and apoptosis in certain cancer cell lines with IC 50 Values ​​are in the nanomolar range. On November 9, 2009, the US Food and Drug Administration approved the marketing of romidepsin injection for the treatment of cutaneous T-cell lymphoma (CTCL). Other indications, such as breast cancer, non-Hodgkin lymphoma, myeloma, ovarian cancer, pancreati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/20C07K1/02
CPCC07K7/06
Inventor 张辉段文凯徐海菊鲍若晗赵国富谭冬婷赵慧凤
Owner TAIZHOU VOCATIONAL COLLEGE OF SCI & TECH
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