半乳糖胺供体的高效经济合成方法研究
Development of an Efficient and Cost-Effective Synthesis Method for Galactosamine Donors
覃子淼 1朱蕴韬1
作者信息
- 1. 江南大学生命科学与健康工程学院，无锡 214122
- 折叠
摘要
半乳糖胺聚糖（galactosaminoglycan）主要分布于多种细菌病原体的细胞壁或细胞膜上，是细菌感染过程中的重要致病因子，这使得其成为新型抗菌疫苗开发的潜力靶点。尽管基于半乳糖胺结构的生物大分子在生物医药领域展现出重要应用价值，但其基础合成砌块D-半乳糖胺的市场价格显著高于其C4-差向异构体D-葡糖胺（价差达两个数量级），这严重制约了相关糖缀合物的规模化制备与功能研究。本研究基于立体选择性合成策略，创新性地开发了以廉价D-葡糖胺为起始原料的半乳糖叠氮硫苷供体（GalN-2）制备路线。通过系统优化保护基策略及关键差向异构化步骤，成功构建了12步线性合成路径，最终以4%的总收率实现目标产物的克级制备。相较于传统合成方法，该路线通过巧妙的原料替代与工艺改进，降低了关键中间体的合成成本，为半乳糖胺类衍生物的大规模制备及其应用于新型糖疫苗研发奠定了重要基础。Abstract
Galactosaminoglycan is predominantly located on the cell walls or membranes of various bacterial pathogens and serves as a crucial virulence factor in bacterial infections, making it a promising target for new antibacterial vaccines. However, the exorbitant cost of D-galactosamine (100-fold pricier than its C4-epimer D-glucosamine) severely hampers scalable production of glycoconjugate therapeutics. Herein, we present a stereoselective synthesis strategy for the donor GalN-2 using the inexpensive D-glucosamine as the starting material. By systematically optimizing the protection group strategy and the key epimerization step, a 12-step linear synthesis pathway was successfully established, ultimately achieving gram-scale preparation of the target product with a total yield of 4%. This innovative methodology reduces synthetic costs by 98% for key intermediates compared to conventional approaches, establishing a practical platform for large-scale preparation of galactosamine derivatives and advancing their translational applications in vaccine development. 关键词
药物化学/D-半乳糖胺/构型翻转Key words
Medicinal Chemistry/D-Galactosamine/Configuration Inversion引用本文复制引用
覃子淼,朱蕴韬.半乳糖胺供体的高效经济合成方法研究[EB/OL].(2025-04-01)[2025-12-13].http://www.paper.edu.cn/releasepaper/content/202504-5.学科分类
药学/生物科学研究方法、生物科学研究技术/制药化学工业
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