Breunig Jamie L, Lin You-Chen, Pierce Joshua G
Department of Chemistry and Integrative Sciences Initiative, NC State University, Raleigh, North Carolina, 27695, United States.
Tetrahedron Lett. 2024 Jul 11;144. doi: 10.1016/j.tetlet.2024.155132. Epub 2024 Jun 8.
Thienamycin is a carbapenem antibiotic with potent activity against gram-negative and gram-positive bacteria. Due to its promising activity but lack of chemical stability, thienamycin serves as inspiration for new synthetic antibiotic scaffolds. In this study, we report a nine-step enantioselective formal synthesis of thienamycin. Our route utilizes an asymmetric reduction, enabled by NaBH and D-tartaric acid, followed by a series of diastereoselective reactions to access the key azetidinone precursor to thienamycin. This azetidinone precursor could be used as an intermediate to further develop and expand the scope of next-generation beta-lactam antibiotic scaffolds.
硫霉素是一种碳青霉烯类抗生素，对革兰氏阴性菌和革兰氏阳性菌具有强大的活性。由于其具有良好的活性但缺乏化学稳定性，硫霉素为新型合成抗生素支架提供了灵感。在本研究中，我们报告了硫霉素的九步对映选择性形式合成。我们的路线利用了由硼氢化钠和D - 酒石酸实现的不对称还原反应，随后进行一系列非对映选择性反应，以获得硫霉素的关键氮杂环丁酮前体。这种氮杂环丁酮前体可作为中间体，用于进一步开发和扩展下一代β - 内酰胺抗生素支架的范围。
