化学
酰胺
产量(工程)
氮气
亲核细胞
组合化学
肽键
氨基酸
保护组
有机化学
肽
立体化学
生物化学
催化作用
材料科学
烷基
冶金
作者
Yuanjun Sun,Wenhao Tang,Mei Wang,Huxin Ni,Ya‐Qiu Long
标识
DOI:10.1002/cjoc.202300106
摘要
Comprehensive Summary Chemically, 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. The key steps include late stage coupling of piperazic acid with 3‐hydroxyleucine derivatives, and HATU‐mediated macrolactamization of 19‐membered macrocycle at N9 and C10. The selective deprotection of N2‐Cbz from the N1,N2‐diCbz‐piperazic acid at late‐stage would greatly facilitate the total syntheses of piperazic acid‐containing cyclodepsipeptides of biological interest.
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