C-GLYCOSIDES VIA THE RAMBERG-BACKLUND REACTION

通过 RAMBERG-BACKLUND 反应生成 C-糖苷

• 批准号: 6526186
• 负责人: RICHARD W. FRANCK
• 金额: $ 23.84万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526186
• 关键词: antineoplastic antibiotics; carbohydrate analog; chemical structure function; drug design /synthesis /production; glycolipids; glycosides

The subject of this research is C-glycosides. These materials are sometimes found in medicinally active natural products, for example papulacandin (anti-fungal) and altromycin B (anti-tumor). There is also intense interest in C-glycosides as analogs of the more commonly found O-glycosides. If they were to be "faithful" analogs, they could interfere in many natural processes normally reserved for O-glycosides with one major difference. C-glycosides would be stable and have a longer lifetime than inherently unstable and shorter-lived O-glycosides. The study of c_glycosides, in most cases, first requires their synthesis in the laboratory. This will be accomplished using a well-established method invented in 1940, but first recognized as useful for carbohydrate chemistry by the PI in 1997. Thus the Ramberg-Backlund reaction will be used to prepare C-glycoside analogs of daunomycin, a clinically active antitumor agent. The northwest sector of altromycin, a powerful antitumor drug, is a natural C-glycoside which has never been prepared in the lab. This is also a target. Further aims include the synthesis of C-glycolipids as analogs of known, bio-active O-glycolipids including KRN7000, an inducer of NK cells. Another aim of this project is the synthesis of C- glyco analogs of disaccharides which include the sialic acid residue. These materials will mimic O-glycosides involved in adhesion in to both respiratory and gastrointestinal epithelial cells.

这项研究的主题是C-糖苷。 这些材料有时在具有药物活性的天然产物中发现，例如乳头状蛋白酶（抗真菌）和非多霉素B（抗肿瘤）。对于更常见的O-糖苷的类似物，对C-糖苷也引起了强烈的兴趣。 如果它们是“忠实”的类似物，它们可能会干扰许多通常保留给O-糖苷的自然过程，其中一个主要区别。 C-糖苷将是稳定的，并且比本质上不稳定且寿命更短的O-糖苷具有更长的寿命。 在大多数情况下，对C_glycosides的研究首先需要在实验室中合成。 这将是使用1940年发明的完善方法来完成的，但首先被PI在1997年被认为对碳水化合物化学有用。因此，Ramberg-backlund反应将用于制备一种临床活性抗肿瘤剂的Daunomycin的C-糖苷类似物。 极强大的抗肿瘤药物是非霉素的西北部门，是一种天然的C-糖苷，从未在实验室中制备。这也是一个目标。 进一步的目的包括将C-糖脂的合成作为已知的生物活性O-糖脂的类似物，包括KRN7000，NK细胞的诱导剂KRN7000。 该项目的另一个目的是合成包括唾液酸残基在内的二糖类似物的合成。 这些材料将模仿与呼吸道和胃肠道上皮细胞相连的O-糖苷。