Cyclic pentapeptide as well as synthetic method and application thereof

A synthetic method, a technique of cyclic pentapeptide, applied in the field of organic chemical synthesis

Active Publication Date: 2014-08-06
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Galaxamide is a new type of cyclic pentapeptide isolated by our research group from the red alga Galaxaura filamentosa collected from Yongxing Island, Xisha Islands, South China Sea (Xu W.J., Liao X.J., Xu S.H., Organic Letters, 2008, 10(20), 4569-4572.), in vitro antitumor activity experiments showed that the compound had 2 And Bel-7402, human breast cancer cell line MCF-7, human cervical cancer cell line Hela and other tumor cells have certain cytotoxicity. At the same time, the mechanism of the compound-induced apoptosis of liver cancer cells Bel-7402 was preliminary studied. The results showed that It shows that Galaxamide is expected to become the lead compound of new anticancer drugs, but the natural products with good activity isolated from natural sources are extremely small, which cannot meet people's needs. It is particularly important to modify the structure and synthesize its analogues

Method used

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  • Cyclic pentapeptide as well as synthetic method and application thereof
  • Cyclic pentapeptide as well as synthetic method and application thereof
  • Cyclic pentapeptide as well as synthetic method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0048] Example 1 Synthesis of tert-butoxycarbonyl-L-leucine (Boc-L-Leu-OH)

[0049] Under nitrogen protection, tetrahydrofuran (THF, 150 mL), H 2 O (100mL) and 1.0mol / L NaOH solution (150mL), add L-leucine (50mmol, 6.55g) in one batch under cooling in an ice-water bath, stir to dissolve evenly, and then add Boc 2 O (60mol, 13.40g), continue to stir in an ice-water bath for 10 minutes, then slowly rise to room temperature, adjust the pH to 10-10.5, stir overnight, evaporate the solvent under reduced pressure, extract with anhydrous ether, and cool the water phase in an ice-water bath and acidified with 1mol / L hydrochloric acid to pH = 2, then extracted 3 times with ethyl acetate, combined the organic phases and washed with saturated brine, anhydrous MgSO 4 After drying and filtering, the solvent was distilled off to obtain white powder tert-butoxycarbonyl-L-leucine with a yield of 98.7%.

Embodiment 2

[0050] Example 2 Synthesis of tert-butoxycarbonyl-D-leucine (Boc-D-Leu-OH)

[0051] The operation of Example 1 was repeated, except that D-leucine was used instead of L-leucine to obtain white powder tert-butoxycarbonyl-D-leucine with a yield of 99.2%.

Embodiment 3

[0052] Example 3 Synthesis of tert-butoxycarbonyl-D-phenylalanine (Boc-D-Phe-OH)

[0053] The operation of Example 1 was repeated except that D-phenylalanine was used instead of L-leucine to obtain transparent oily tert-butoxycarbonyl-D-phenylalanine with a yield of 98.5%.

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Abstract

The invention belongs to the field of organic chemical synthesis, and discloses cyclic pentapeptide with a novel structure, as well as a synthetic method and application thereof. The cyclic pentapeptide with the novel structure is cyclo-(N-Me-D-Phe-D-Leu-N-Me-D-Leu-D-Leu-L-Leu), the molecular formula is C35H57N5O5, and the structural formula is shown in the description. The cyclic pentapeptide adopts D-Leu, L-Leu, D-Phe and D-Leu benzyl ester tosilate as raw materials, a tripeptide midbody and a dipeptide midbody are respectively prepared through a proper technology, and a cyclization locus is selected at the amido linkage position adjacent to D and L configurations, so that the cyclization efficiency is effectively increased. The cyclic pentapeptide has the advantages of simple synthetic process, low raw material cost, mild reaction conditions, high purity and easy industrial production, and can fully meet the requirements of medical experiments and clinical application.

Description

technical field [0001] The invention belongs to the field of organic chemical synthesis, and specifically relates to a cyclopentapeptide and its synthesis method and application. Background technique [0002] Cyclic peptides are widely found in nature. Plants, animals, lower marine organisms, microorganisms, bacteria and pathogens contain trace amounts of cyclic peptides. Although the content of these cyclic peptides is low, their specific structure and pharmacological effects are unmatched by terrestrial organisms. Natural cyclic peptide compounds have remarkable pharmacological stability and potency, and relatively small toxicological effects. They have unique effects on the prevention and treatment of cancer, AIDS, cardiovascular and cerebrovascular diseases, geriatric diseases and other intractable diseases. One of the main directions of medicine. [0003] Due to the lack of free N-terminal and C-termini, cyclic peptides can form restricted conformations. Generally sp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K11/02C07K1/06A61K38/12A61P35/00
Inventor 徐石海邱少玲肖茜白德发
Owner JINAN UNIVERSITY
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