Total Synthesis and Stereochemistry Revision of Mannopeptimycin Aglycone

被引：34

作者：

Fuse, Shinichiro ^{[1
]}

Koinuma, Hirotsugu ^{[1
]}

Kimbara, Atsushi ^{[1
]}

Izumikawa, Miho ^{[2
]}

Mifune, Yuto ^{[1
]}

He, Haiyin ^{[3
]}

Shin-ya, Kazuo ^{[4
]}

Takahashi, Takashi ^{[5
]}

Doi, Takayuki ^{[6
]}

机构：

[1] Tokyo Inst Technol, Dept Appl Chem, Meguro Ku, Tokyo 1528552, Japan

[2] Japan Biol Informat Consortium JBIC, Koto Ku, Tokyo 1350064, Japan

[3] Pfizer Worldwide Res & Dev, Nat Prod Lab, Worldwide Med Chem, Groton, CT 06340 USA

[4] Natl Inst Adv Ind Sci & Technol, Koto Ku, Tokyo 1350064, Japan

[5] Yokohama Coll Pharm, Totsuka Ku, Yokohama, Kanagawa 2450066, Japan

[6] Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2014年 / 136卷 / 34期

关键词：

ANTI-TUMOR ACTIVITY; ALPHA-AMINO-ACIDS; STREPTOMYCES-HYGROSCOPICUS; ASYMMETRIC-SYNTHESIS; ANTIBIOTICS; DERIVATIVES; GLYCOPEPTIDES; PRUMYCIN; ENDURACIDIDINE; ANTIBACTERIAL;

D O I：

10.1021/ja505105t

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Development of efficient methods for preparation of bioactive nonribosomal peptides, containing densely functionalized nonproteinogenic amino acids, is an important task in organic synthesis. We have employed a concise synthesis for such amino acids by asymmetric aldol addition coupled with an isomeric resolution via diastereoselective cyclization. This approach is successfully applied to the first total synthesis of the cyclic hexapeptide aglycone of the mannopeptimycins, a group of glycopeptides known for potent activity against drug-resistant bacteria. The facile preparation of the key amino acids and the synthesis of the aglycone pave the way for further studies on this class of antibiotics and the development of new lead compounds with therapeutic potential. In addition, our studies have led to the revision of the stereochemistry of the,beta-methylphenylalanine residue in the mannopeptimycin aglycone.

引用

页码：12011 / 12017

页数：7

共 51 条

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