INTRAMOLECULAR C-GLYCOSIDATION OF SUBSTITUTED SUGARS

取代糖的分子内 C-糖苷化

• 批准号: 3295322
• 负责人: OLIVIER R MARTIN
• 金额: $ 7.22万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3295322
• 关键词: aminosugar; antiviral agents; benzene; benzofurans; carbohydrates; chemical reaction; chemical substitution; flavonoids; glycosides; hydroxyl group; isoquinolines; molecular biology; stereochemistry

A novel methodology for the stereospecific synthesis of C- glycosides is proposed. This methodology is based on the preliminary attachment of a substituent containing a latent carbon-nucleophilic function to one of the hydroxyl function of a cyclic sugar derivative, followed by the creation of a carbon- carbon bond between this group and the anomeric center of the sugar. Thus, O-benzylated, N-benzylated and O-phenylated sugars should lead to "internal" C-glycosides (isochromans, tetrahydroisoquinolines and 2,3-dihydrobenzofurans resp.) which could be cleaved to C-glycosylated benzene derivatives or further elaborated (for example into tetrahydroisoquinoline alkaloids). The one-step transfer of a C-nucleophile might be achieved using a difunctional silyl derivative as a temporary linkage to the sugar- hydroxyl function: thus O-aryloxysilyl, as well as O-aryl-and O- allyl-dimethylsilyl carbohydrate derivatives are expected to undergo intra-molecular C-glycosidation with simultaneous cleavage of the auxiliary linkage upon treatment with a Lewis acid, thereby providing a highly efficient and general method of stereospecific C-glycosidation. This methodology will be used for the synthesis of a number of biologically and pharmacologically significant structures. Thus a series of arabino nucleoside analogs, in particular the dideaza analog of ara-C, one of the most potent agents against acute leukemia, benzenoid analogs of cyclouridine and cyclocytidine, as well indole C-nucleosides related to the antiviral agent are-A will be prepared by the intramolecular C-glycosylation of suitably substituted benzene and indole derivatives. The proposed methodology provides also a short approach to natural internal C- glycosides such as bergenin and related compounds, as well as to C-glycosyl flavonoids. Furthermore, N-benzylated amino sugars are precursors of chiral tetrahydroisoquinolines which have an extremely interesting substitution pattern because of its relation to that of tetra-hydroisoquinolines derived from biogenic amines and certain psychopharmacological drugs. C-benzylation of the corresponding N-benzylidene imino sugars, expected to be highly stereoselective, gives an intermediate which should lead in one step, by a "double intramolecular C-arylation" process, to the skeleton of the isopavine alkaloids. These reactions provide a short synthetic route from carbohydrates to chiral tetra- hydroisoquinoline alkaloids.

一种立体定向合成C- 糖基化被提出。 该方法基于 含有潜在的取代基的初步连接 碳-亲核官能团连接到 环糖衍生物，然后是碳- 该基团和异头中心之间的碳键 糖 因此，O-苄基化、N-苄基化和O-苯基化的糖 应该导致"内部" C-糖苷（异色满， 四氢异喹啉和2，3-二氢苯并呋喃）这 可以裂解成C-糖基化苯衍生物或进一步 精制（例如，制成四氢异喹啉生物碱）。 C-亲核试剂的一步转移可以使用 作为与糖的临时连接的双官能甲硅烷基衍生物， 羟基官能团：因此是O-芳氧基甲硅烷基，以及O-芳基-和O- 预期烯丙基-二甲基甲硅烷基碳水化合物衍生物 进行分子内C-糖苷化，同时 用刘易斯处理时辅助键的断裂 酸，从而提供了高效和通用的方法， 立体特异性C-糖苷化。 这一方法将用于综合若干 具有生物学和生物学意义的结构。 因此 一系列阿拉伯核苷类似物，特别是二脱氮 阿糖胞苷的类似物，一种最有效的抗急性 白血病，环胞苷和环胞苷的苯型类似物，如 那么吲哚C-核苷类相关的抗病毒剂是-A将 通过适当的分子内C-糖基化来制备 取代的苯和吲哚衍生物。 拟议 方法也提供了一个简短的方法，自然的内部C- 糖苷如岩白菜素和相关化合物，以及 C-糖基类黄酮。 此外，N-苄基化氨基糖 是手性四氢异喹啉的前体， 非常有趣的替代模式，因为它的关系 衍生自生物胺的四氢异喹啉 和某些精神药物 C-苄基化 相应的N-亚苄基亚氨基糖，预计高度 立体选择性，得到一种中间体， 步骤，通过"双分子内C-芳基化"过程， 异罂粟碱生物碱的骨架。 这些反应提供了 从碳水化合物到手性四氢呋喃的短合成路线 氢异喹啉生物碱。