文献类型：期刊文献

英文题名：Total Synthesis of Mannopeptimycins α and β

作者：Wang, Bo[4];Liu, Yunpeng[4,5];Jiao, Rui[4,7];Feng, Yiqing[4,6];Li, Qiong[4,8];Chen, Chen[4];Liu, Long[1,2];He, Gang[1,2,3];Chen, Gong[1,2,3,4]

机构：[1]Nankai Univ, State Key Lab, Tianjin 300071, Peoples R China;[2]Nankai Univ, Inst Elementoorgan Chem, Tianjin 300071, Peoples R China;[3]Collaborat Innovat Ctr Chem Sci & Engn Tianjin, Tianjin 300071, Peoples R China;[4]Penn State Univ, Dept Chem, University Pk, PA 16802 USA;[5]Georgia State Univ, Dept Chem, Atlanta, GA 30302 USA;[6]Pfizer Inc, Worldwide MedChem, Groton, CT 06340 USA;[7]Lianyungang Teachers Coll, Nanjing 22066, Jiangsu, Peoples R China;[8]E China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China

年份：2016

卷号：138

期号：11

起止页码：3926

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20161402204685);WOS:【SCI-EXPANDED(收录号:WOS:000372854200042)，CCR-EXPANDED(收录号:WOS:000372854200042)】；

基金：We gratefully thank The Pennsylvania State University and the State Key Laboratory of Elemento-Organic Chemistry at Nankai University for financial support of this work. We dedicate this work to Prof. Samuel J. Danishefsky on the occasion of his 80th birthday.

语种：英文

外文关键词：Palladium compounds - Scaffolds - Catalysis - Synthesis (chemical)

摘要：The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. Their cyclic hexapeptide core features a pair of unprecedented beta-hydroxyenduracididines (L- and D-beta hEnd), an O-glycosylated D-Tyr carrying an alpha-linked dimannose, and a beta-methylated Phe residue. The D-beta hEnd unit also carries an alpha-linked mannopyranose at the most hindered N of its cyclic guanidine ring. Herein, we report the first total synthesis of mannopeptimycin alpha and beta with fully elaborated N- and O-linked sugars. Critically, a gold-catalyzed N-glycosylation of a D-beta hEnd substrate with a mannosyl ortho-alkynylbnzoate donor enabled the synthesis of the most challenging N-Man-D-beta hEnd unit with excellent efficiency and stereoselectivity. The L-beta MePhe unit was prepared using a Pd-catalyzed C-H arylation method. The L-beta hEnd, D-Tyr(di-Man), and L-beta MePhe units were prepared in gram quantities. A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin alpha and beta.