Synthesis of the disaccharide moiety of bleomycin
文献类型：期刊论文
| 作者 | Cai Juntao1; Liu Zhonghua1; Zou Xiaopeng1; Guo Xiaoqiang1; Chen Yuelei2 ; Xiong Bing2; Shen Jingkang2; Nakanishi Hideki1; Yin Jian1
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| 刊名 | Chinese Journal of Medicinal Chemistry
 |
| 出版日期 | 2016 |
| 卷号 | 26期号:6页码:457-465 |
| 关键词 | disaccharide glycosylation targeting gulose protecting group |
| ISSN号 | 1005-0108 |
| 其他题名 | 博来霉素二糖片段合成研究 |
| 文献子类 | Article |
| 英文摘要 | The bleomycins(BLM)are the major constituent of a family of glycopeptide antitumor antibiotics first isolated from Streptomyces verticillus,which are thought to exert their biological effects through a metal dependent oxidative cleavage of DNA or RNA in the presence of oxygen. It shows high anti-tumor activity and is used as one of the fist-line antitumor drugs for a long time in clinical settings. Recently, scientists have discovered that the disaccharide moiety was responsible for the tumor cell targeting properties of bleomycin. The disaccharide moiety have been designed and synthesized by a number of research groups. In this paper, we have developed a new convenient method for the synthesis of 3-O-carbamoyl-alpha-D-mannopyranosyl. Starting from unexpensive and commercially available D-mannose,4,6-O-benzylidene-2-O-acetyl-3-Ocarbamoyl-alpha-D-mannopyranose 3 was achieved in the linear 6 steps with 28% overall yield. p-Tolyl 3,4,6-tri-O-benzyl-alpha,beta-L-thio-gulopyranose 4 was prepared from methyl-alpha-D-glucopyranoside in 13 steps with 8% overall yield. The chemical synthesis of 2-O-(3-O-carbamoyl-alpha-D-mannopyranosyl)-L-gulopyranose was readily adaptable to the preparation of structural analogs. The precursor disaccharide 2 was obtained in a diastereospecific glycosidation of building block 3 with the alpha-glycosyl of building block 4,which proceeded in exceptionally good yield(83%)with net retention of the alpha-D-mannopyranosyl C-1 stereochemistry. All the new compounds were characterized by IR,~1H-NMR,~(13)C-NMR and HRMS data. Next, the precursor disaccharide as a glycosyl donor was conjugated with the fluorescent molecules or other cytotoxin to explore their biological activity. |
| 资助项目 | 国家自然科学基金项目[00000000] ; 江苏省自然科学基金项目[00000000] ; 科技重大专项重大新药创制基金项目[00000000] ; 中央高校基本科研业务费专项资金项目[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy (provided by Clarivate Analytics) |
| 语种 | 中文 |
| CSCD记录号 | CSCD:5893199 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/269219]  |
| 专题 | 药物化学研究室 |
| 作者单位 | 1.Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education, School of Biotechnology,Jiangnan University, Wuxi, Jiangsu 214122, China.; 2.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. |
| 推荐引用方式 GB/T 7714 | Cai Juntao,Liu Zhonghua,Zou Xiaopeng,et al. Synthesis of the disaccharide moiety of bleomycin[J]. Chinese Journal of Medicinal Chemistry,2016,26(6):457-465. |
| APA | Cai Juntao.,Liu Zhonghua.,Zou Xiaopeng.,Guo Xiaoqiang.,Chen Yuelei.,...&Yin Jian.(2016).Synthesis of the disaccharide moiety of bleomycin.Chinese Journal of Medicinal Chemistry,26(6),457-465. |
| MLA | Cai Juntao,et al."Synthesis of the disaccharide moiety of bleomycin".Chinese Journal of Medicinal Chemistry 26.6(2016):457-465. |
入库方式： OAI收割
来源：上海药物研究所
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