Synthesis method of daptomycin

A synthesis method and technology of daptomycin are applied in the field of daptomycin synthesis of solid-liquid phase combination, which can solve the problem of high synthesis cost and achieve the desired effect.

Active Publication Date: 2008-08-06
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI +1
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

It mainly solves the existing technical problem that the synthesis cost is too high using Streptomyces roseospora as the raw material

Method used

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  • Synthesis method of daptomycin
  • Synthesis method of daptomycin

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Experimental program
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Embodiment

[0048] Synthesis of Daptomycin

[0049]

[0050] 1.1 Solid-phase preparation of fully protected peptides

[0051] Weigh 0.5 g of 2-Cl-Chlorotrityl Chloride resin (0.4-0.5 mmol / g), soak it in 100 ml of DMF to fully swell the resin, and drain it. Take 0.15g of Fmoc-Gly-OH and put it into a peptide bottle, dissolve it in 60ml of DMF, add 0.6ml of DIEA, and react at 25°C for 1 hour. Drained and added 60ml of methanol to react for 10min. Drained, respectively with DMF, MeOH, CH 2 Cl2 and Et 2 O were washed three times each and dried. Weighed 0.081g. The degree of substitution was 0.54 mmol / g.

[0052] Put the above resin into a peptide bottle, add 50ml of 20% piperidine (DMF), shake for 5min, and drain. Then add 50ml of 20% piperidine (DMF) and shake for 15min, then suck dry, wash with DMF, MeOH and CH 2 Cl 2 Each was washed three times in turn, and then followed by Fmoc-Asp(O t Bu)-OH, Fmoc-D-Ala-OH, Fmoc-Asp(O t Bu)-OH, Fmoc-Orn(Boc)-OH, Fmoc-Gly-OH, Fmoc-Thr-OH, Fm...

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Abstract

The invention relates to a daptomycin synthesis method for resolving the technical problem of prior art which uses rose spore streptomycete as raw material to cost high synthesis cost. The synthesis method comprises a, using 2-chlorine trityl chloride resin as carrier, via solid synthesis method to connect the amino acids with protective groups, to obtain protective decapeptide resin while the Fmoc-protective groups are removed in turn, B, connecting decanoic acid via same method, connecting next amino acid via esterification, removing Fmoc-protective groups, and connecting left two amino acids via normal solid method, removing Fmoc-protective groups, c, using trifluoroacetic acid or carrene solution to cut off total protective peptide from resin, drying and completing end-to-end liquid cyclisation in organic solvent, d, using the mixture of trifluoroacetic acid, water and benzene methyl sulfide to cut off peptide from resin to obtain crude product. The invention can synthesize daptomycin.

Description

Technical field: [0001] The invention relates to a method for synthesizing novel antibiotic Daptomycin. In particular, it relates to a method for synthesizing daptomycin with solid-liquid combination. Background technique: [0002] In recent years, with the increasing use of antibiotics, the problem of bacterial resistance has become increasingly serious. In the United States, 95% of clinically isolated S. aureus are resistant to penicillin, and more than 50% are resistant to methicillin (FrindkinSK, Gaynes RP. Antimicrobial resistance in intensive care units. ClinChest Med.1999, 20 (2) : 303-316); in Japan, the proportion of methicillin-resistant Staphylococus aureus (MRSA) strains from skin infections during the past three years. J Dermatil, 1993, 20(4): 193-197). Although vancomycin is often considered as the last line of defense against Gram-positive bacterial infections, this line of defense is not indestructible. Since the 1980s, there has been an increase in vancom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K1/04
CPCY02P20/55
Inventor 徐红岩陆婷婷
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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