Lennard-Jones Laboratories, School of Chemical and Physical Sciences, Keele University, ST5 5BG, Staffordshire, UK.
Chem Rec. 2021 Nov;21(11):3238-3255. doi: 10.1002/tcr.202100173. Epub 2021 Sep 15.
Heparin and heparan sulfate represent key members of the glycosaminoglycan family of carbohydrates and underpin considerable repertoires of biological importance. As such, their efficiency of synthesis represents a key requirement, to further understand and exploit the H/HS structure-to-biological function axis. In this review we focus on chemical approaches to and methodology improvements for the synthesis of these essential sugars (from 2015 onwards). We first consider advances in accessing the heparin-derived pentasaccharide anticoagulant fondaparinux. This is followed by heparan sulfate targets, including key building block synthesis, oligosaccharide construction and chemical sulfation techniques. We end with a consideration of technological improvements to traditional, solution-phase synthesis approaches that are increasingly being utilised.
肝素和硫酸乙酰肝素是糖胺聚糖家族碳水化合物的主要成员,为许多重要的生物学功能奠定了基础。因此,它们的高效合成是进一步理解和利用 H/HS 结构与生物学功能关系的关键需求。在这篇综述中,我们重点关注从 2015 年开始的这些重要糖的化学合成方法和方法学改进。我们首先考虑了获得肝素衍生的戊糖抗凝剂磺达肝素的方法的进展。接着讨论了硫酸乙酰肝素的靶标,包括关键结构单元的合成、寡糖的构建和化学硫酸化技术。最后,我们考虑了对传统溶液相合成方法的技术改进,这些方法正越来越多地被应用。