Uncommon Sugars and Their Glycosylation

该项目的重点是开发一种闭合环复分解（RCM）方法，以产生一个小的不常见糖库。通过使用相应的1,2-糖库作为中间体，将使不常见的糖库更适合下一步的立体选择性糖基化。一些新的“硫试剂”将被开发出来，用于通过SN2'-同步机制将L-或d -鼠李醛或L-或d -3-甲基鼠李醛转化为β -1-硫-2-假糖。从8个α - &amp； β -1-硫代-2-假糖基，可以通过常规立体定向转化将C4位置功能化或通过新的硫酰化化学将C3位置功能化来制备32个糖基。从糖库中，将合成1- s -2-轴- i供体和新的1-S-2-eq-（2-吡啶硫代）供体，并评估它们将2-杂原子糖1-硫代糖苷连接到具有特定α或β构型的糖醛基上。这种立体特异性糖基化方法将在迭代一锅法中用于合成新型抗生素Saccharimicins中低聚糖的17个成员。通过这个奖项，有机和大分子化学项目支持了俄亥俄州立大学生物化学系王鹏教授的研究。王教授和他的学生们正在开发新的化学和新的试剂来合成具有巨大结构多样性的罕见糖。不常见的糖，包括脱氧糖、氨基脱氧糖和支链糖，通常存在于微生物和植物的次生代谢物中，如心糖苷、抗生素和抗癌剂。这些具有重要药理意义的代谢产物的糖部分在决定这些天然产物的生物活性方面起着重要作用。由于罕见糖在含糖生物活性天然产物和药物的构效关系研究中具有重要意义，本研究将为药物化学和制药工业提供通用的化学平台和技术。

This project is focused on the development of a ring closing metathesis (RCM) approach to produce a small library of uncommon sugars. By using a corresponding 1,2-glycal library as intermediates, the uncommon sugar library will be made more amenable for stereoselective glycosylation in the next step. Several new "thio-reagents" will be developed for the conversion of L- or D-rhamnal or L- or D-3-methylrhamnal to beta-1-thio-2-pseudoglycal through a SN2'-syn mechanism. From 8 alpha- & beta-1-thio-2- pseudoglycals, 32 glycals can be prepared by either functionalization of the C4 position through routine stereospecific transformations or/and by functionalization of C3 position through new sulfimidation chemistry. From the glycal library, 1-S-2-axial-I donors and novel 1-S-2-eq-(2- picolylthio) donors will be synthesized and evaluated for connecting the 2-heteroatom sugar 1-thioglycoside to an aglycon with specific alpha or beta configuration. This stereospecific glycosylation method will be used in an iterative one-pot approach to synthesize the 17 members of oligosaccharide in novel antibiotic Saccharimicins.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Peng G. Wang, of the Department of Biochemistry at the Ohio State University. Professor Wang and his students are developing new chemistry and new reagents for the synthesis of uncommon sugars with great structural diversity. Uncommon sugars, which include deoxysugars, amino deoxysugars and branched-chain sugars, are frequently found in the secondary metabolites of microorganisms and plants, such as cardioglycosides, antibiotics, and anticancer agents. The sugar moieties of these pharmaceutically important metabolites play an important role in determining the biological activities of these natural products. Since uncommon sugars are extremely useful in the structure-activity-relationship (SAR) study of sugar containing bioactive natural products and pharmaceuticals, this research will provide a general chemistry platform and technology for medicinal chemistry and pharmaceutical industry.