Total Synthesis and Antibacterial Investigations of 1‐Hydroxyboivinianin A
Total Synthesis and Antibacterial Investigations of 1‐Hydroxyboivinianin A
复制标题
1-羟基boivinianin A的全合成及抗菌研究
DOI：
10.1002/cmdc.202200363
复制
发表时间：
2022
期刊：
影响因子：
3.4
通讯作者：
Wuest, William M.
中科院分区：
文献类型：
--
作者：
Wilt, Ingrid K.;Demeritte, Adrian R.;Wang, Weiwei;Wuest, William M.
天然产物的合成研究有助于开发新型抗菌小分子。1-hydroxyboivinianin A是一种从海洋沉积物中分离出的含有酚类没药烷的内酯，已报道对水生病原体哈氏弧菌具有抗菌活性。1-羟基boivinianin A及其对映体的全合成以42%的总收率在六步序列中完成。该合成利用与手性咪唑烷酮的关键非对映选择性亲核加成来建立苄型叔醇，并利用分子内Horner沃兹沃斯埃蒙斯来提供内酯。发现两种对映体对一组革兰氏阳性和阴性细菌的抗菌活性可以忽略不计，对植物病原体的抗真菌活性也很小。对可能在玻璃体内内酯水解产生无活性线性酸的研究发现了自发环化，表明内酯对水解具有抗性，并且内酯不会降解产生无活性物质。
Synthetic investigations of natural products has been instrumental in the development of novel antibacterial small molecules. 1‐hydroxyboivinianin A, a lactone containing phenolic bisabolane isolated from marine sediment, has reported antibacterial activity against the aquatic pathogenVibrio harveyi. The total synthesis of 1‐hydroxyboivinianin A and its enantiomer was completed in a six‐step sequence in 42 % overall yield. The synthesis leveraged a key diastereoselective nucleophilic addition with chiral imidazolidinone to establish the benzylic tertiary alcohol and intramolecular Horner‐Wadsworth Emmons to furnish the lactone. Both enantiomers were found to have negligible antibacterial activity against a panel of gram‐positive and negative bacteria and minimal antifungal activity against phytopathogens. Investigations of a possiblein vitrolactone hydrolysis to produce an inactive linear acid led to the discovery of a spontaneous cyclization, suggesting the lactone is resistant to hydrolysis and the lactone is not degrading to produce an inactive species.