海洋环肽stylissamide Ⅰ的全合成研究

陆东涛; 刘超; 秦路平; 邹燕

doi:10.3969/j.issn.1006-0111.2019.05.011

海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011

1.
海军军医大学长海医院药材科, 上海 200433
2.
海军军医大学药学院, 上海 200433

基金项目: 海军军医大学军事课题（2017JS11）

The total solid synthesis of marine cyclopeptide stylissamide Ⅰ

1.
Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai 200433, China
2.
School of Pharmacy, Naval Medical University, Shanghai 200433, China

摘要: 目的采用固相合成/液相环化方法合成海洋环肽stylissamide Ⅰ。方法以2-氯三苯甲基氯树脂（简称二氯树脂）为载体，选用6-氯苯并三氮唑-1，1，3，3-四甲基脲六氟磷酸酯（HCTU）和N，N-二异丙基乙胺（DIPEA）为缩合试剂依次连接9-笏甲氧羰基保护的氨基酸，在三氟乙醇（TFE）的作用下将直链肽从树脂上切割下来，然后使用（3H-1，2，3-三唑并吡啶-3-氧基）三-1-吡咯烷基六氟磷酸盐（PyAOP），N-羟基-7-氮杂苯并三氮唑（HOAt）和N-甲基吗啡啉（NMM）在溶液中完成环合，最后在三氟乙酸（TFA）的处理下脱去侧链保护基，获得环肽粗品。经反相高效液相色谱对所合成的环肽粗品进行纯化，终产物纯度98.9%。通过高分辨质谱、600 MHz ¹H-NMR和¹³C-NMR鉴定，确定所合成环肽为目标环肽。结果首次完成海洋环肽stylissamide Ⅰ的全合成，总收率为67%。结论此法具有快捷、简便、高效的特点，较好地为stylissamide Ⅰ的固相全合成提供了参考。
- stylissamideⅠ /
- 固相合成 /
- 环肽
Abstract: Objective The marine cyclopeptide stylissamide Ⅰ was synthesized through a solid phase synthesis and cyclization in solution(SPS-CS). Methods 2-chlorotrityl chloride resin was used as solid support for the total synthesis.Each amino acid protected by 9-fluorenylmethyloxycarbonyl(Fmoc) group was coupled with N,N-diisopropylethylamine(DIPEA)/O-(6-chloro-1-hydrocibenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluoro- phosphat(HCTU) as condensing agents.The linear peptide was cleaved from resin by 2,2,2-trifluoroethanol(TFE) and cyclized in the presence of(7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate(PyAOP)/1-hydroxy-7-azabenzotriazole(HOAt)/N-methyl morphofine(NMM).Finally,the crude cyclopeptide was obtained through global deprotection with trifluoroacetic acid(TFA).The target compound was purified by preparative RP-HPLC to 98.9% pure and its structure was identified by ¹H-NMR,¹³C-NMR and Q-TOF LC/MS. Results The first total synthesis of the marine cyclopeptide stylissamide Ⅰ was successfully realized with a yield of 67%. Conclusion A rapid,simple and high-efficient method of stylissamide Ⅰ total synthesis was successfully established.
- stylissamide Ⅰ /
- solid phase synthesis /
- cyclopeptide

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海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011

The total solid synthesis of marine cyclopeptide stylissamide Ⅰ

计量

海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011

1. 海军军医大学长海医院药材科, 上海 200433

2. 海军军医大学药学院, 上海 200433

English Abstract

The total solid synthesis of marine cyclopeptide stylissamide Ⅰ

1. Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai 200433, China

2. School of Pharmacy, Naval Medical University, Shanghai 200433, China

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留言板

海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011

The total solid synthesis of marine cyclopeptide stylissamide Ⅰ

计量

出版历程

海洋环肽stylissamide Ⅰ的全合成研究

doi: 10.3969/j.issn.1006-0111.2019.05.011

1. 海军军医大学长海医院 药材科, 上海 200433 2. 海军军医大学 药学院, 上海 200433

English Abstract

The total solid synthesis of marine cyclopeptide stylissamide Ⅰ

1. Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai 200433, China 2. School of Pharmacy, Naval Medical University, Shanghai 200433, China

全文HTML

目录

1. 海军军医大学长海医院药材科, 上海 200433

2. 海军军医大学药学院, 上海 200433

1. Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai 200433, China

2. School of Pharmacy, Naval Medical University, Shanghai 200433, China