Comprehensive SummaryChemically,N1 nitrogen of piperazic acid is more nucleophilic than N2 nitrogen,but amide bonds predominantly formed at N2 nitrogen are prevalent in piperazic acid-containing natural products,with ...Comprehensive SummaryChemically,N1 nitrogen of piperazic acid is more nucleophilic than N2 nitrogen,but amide bonds predominantly formed at N2 nitrogen are prevalent in piperazic acid-containing natural products,with only one exception of sanglifehrin.Thus two orthogonal protecting groups of nitrogen are often employed to realize selective coupling of N2 nitrogen,resulting in increased synthetic steps and low synthetic efficiency.However,we develop selective deprotection of N2-Cbz from the N1,N2-diCbz-piperazic acid-containing peptide to form the N2 amide exclusively,avoiding the tedious orthogonal protection strategy which is commonly applied when the easily-accessible N1,N2-diCbz-piperazic acid is used as the synthetic module.We employ this selective-deprotection strategy to achieve an efficient synthesis of piperazic acid-containing cyclodepsipeptide core of verucopeptin with an overall yield of 21%from commercially/readily available building blocks.展开更多
基金supported by the National Natural Science Foundation of China(No.22207081)National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(No.2018Zx09711002-006-004)+1 种基金China National Postdoctoral Program for Innovative Talents(No.BX20200232)China Postdoctoral Science Foundation(No.2020M681725).
文摘Comprehensive SummaryChemically,N1 nitrogen of piperazic acid is more nucleophilic than N2 nitrogen,but amide bonds predominantly formed at N2 nitrogen are prevalent in piperazic acid-containing natural products,with only one exception of sanglifehrin.Thus two orthogonal protecting groups of nitrogen are often employed to realize selective coupling of N2 nitrogen,resulting in increased synthetic steps and low synthetic efficiency.However,we develop selective deprotection of N2-Cbz from the N1,N2-diCbz-piperazic acid-containing peptide to form the N2 amide exclusively,avoiding the tedious orthogonal protection strategy which is commonly applied when the easily-accessible N1,N2-diCbz-piperazic acid is used as the synthetic module.We employ this selective-deprotection strategy to achieve an efficient synthesis of piperazic acid-containing cyclodepsipeptide core of verucopeptin with an overall yield of 21%from commercially/readily available building blocks.
