【摘要】 肺结核是严重的全球性公共卫生问题,尤其是耐药结核病的流行,使得传统治疗方案面临巨大挑战.贝达喹啉作为一类新型抗结核药物,为耐药结核病的治疗提供了重要选择.然而,该分子连续三取代和四取代的手性中心的构建对合成工艺提出了较高要求.因此,开发高效、绿色的不对称合成工艺成为研究热点.综述了贝达喹啉类药物的合成工艺进展,重点探讨了双金属协同催化策略等关键技术路径.此外,连续流合成技术作为一种新兴工艺,因其高效、安全及易于放大等优势,在制备贝达喹啉工艺中展现出巨大潜力.未来,结合新型催化体系、绿色化学及智能化生产技术的开发,贝达喹啉类药物的合成工艺将朝着更高效环保的方向发展,为抗结核药物的规模化生产提供重要支持.更多还原

【Abstract】 Tuberculosis remains a significant global public health concern, particularly due to the increasing prevalence of drug-resistant tuberculosis, which poses substantial challenges to traditional treatment strategies. Bedaquiline, a novel class of anti-tuberculosis drug, offers a critical alternative for managing drug-resistant tuberculosis. However, the synthesis of this compound is one of the greatest challenges in synthetic chemistry due to its contiguous tertiary and tetrasubstituted chiral centers, necessitating advanced synthetic methodologies. Consequently, the advancement of efficient and environmentally sustainable asymmetric synthesis technologies has emerged as a key research priority. This review summarizes the synthetic pathways of bedaquiline, with an emphasis on pivotal technological approaches such as bimetallic catalysis. Furthermore, continuous flow technology, owing to its inherent advantages of efficiency, safety, and scalability, demonstrates considerable promise in the production of bedaquiline. Looking ahead, the integration of innovative catalytic systems, green chemistry principles, and intelligent manufacturing technologies will likely drive the evolution of bedaquiline synthesis toward greater efficiency and environmental compatibility, thereby facilitating large-scale production of anti-tuberculosis medications.更多还原