500145-45-9Relevant academic research and scientific papers
Ahp-Cyclodepsipeptide Inhibitors of Elastase: Lyngbyastatin 7 Stability, Scalable Synthesis, and Focused Library Analysis
Luo, Danmeng,Luesch, Hendrik
, p. 419 - 425 (2020)
Due to the potency and selectivity of lyngbyastatin 7 in inhibiting neutrophil elastase, a serine protease involved in numerous diseases, this cyclodepsipeptide was considered as a promising lead and subjected to further developmental studies. Lyngbyastat
Total Synthesis of the Potent Marine-Derived Elastase Inhibitor Lyngbyastatin 7 and in Vitro Biological Evaluation in Model Systems for Pulmonary Diseases
Luo, Danmeng,Chen, Qi-Yin,Luesch, Hendrik
, p. 532 - 544 (2016/01/25)
Lyngbyastatin 7 (1) is a marine cyanobacteria-derived lariat-type cyclic depsipeptide of which the macrocyclic core possesses modified amino acids, including a featured 3-amino-6-hydroxy-2-piperidone (Ahp) moiety and a (Z)-2-amino-2-butenoic acid (Abu) moiety. The first total synthesis of 1 was successfully established via 31 steps, and the conditions of several crucial steps were optimized to ensure smooth operations. The previously reported structural assignment and elastase inhibitory activity of the isolated natural product were confirmed. According to the extensive in vitro biological evaluation, compound 1 displayed low nanomolar IC50 in blocking elastase activity and strong ability in protecting bronchial epithelial cells against elastase-induced antiproliferation and abrogating the elastase-triggered induction of pro-inflammatory cytokine expression. Its overall performance was superior over sivelestat, the only approved small molecule drug targeting elastase, which indicated its potential in developing as a pharmacotherapeutic against elastase-mediated pathologies. The success in total synthesis, designed with a novel convergent strategy, not only overcame the supply issue for thorough preclinical studies but also paved the way for convenient synthesis of analogues with improved potency and druglike properties.
Total synthesis of somamide A, an Ahp (3-amino-6-hydroxy-2-piperidone)-containing cyclic depsipeptide
Yokokawa, Fumiaki,Shioiri, Takayuki
, p. 8673 - 8677 (2007/10/03)
The first total synthesis of somamide A (1), an Ahp (3-amino-6-hydroxy-2-piperidone)-containing cyclic depsipeptide, from the marine cyanobacterium Lyngbya majuscula is described. The efficient and stereospecific dehydration of the N-acyl threonine ester using Martin's sulfurane provided the (Z)-2-amino-2-butenoic acid residue. The macrolactamization using FDPP(Ph2P(O)OC6F5), the final installation of the Ahp moiety by oxidation with 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide, and cyclization of the norvaline derivative to the cyclic hemiaminal afforded somamide A (1).
