INTRAMOLECULAR C-GLYCOSIDATION OF SUBSTITUTED SUGARS

一种立体定向合成 C- 的新方法 建议配糖体。 该方法基于 初步连接含有潜在的取代基 碳亲核官能团与羟基官能团之一 环糖衍生物，然后创建碳- 该基团与异头中心之间的碳键 糖。 因此，O-苯甲基化、N-苯甲基化和O-苯基化糖 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） 可以裂解成C-糖基化苯衍生物或进一步 精制（例如四氢异喹啉生物碱）。 C-亲核试剂的一步转移可通过以下方法实现 双官能硅基衍生物作为糖的临时连接 羟基官能团：因此O-芳氧基甲硅烷基，以及O-芳基-和O- 烯丙基二甲基甲硅烷基碳水化合物衍生物预计 同时进行分子内 C-糖苷化 用路易斯处理后辅助键的断裂 酸，从而提供了一种高效且通用的方法 立体特异性C-糖苷化。 该方法将用于合成许多 具有生物学和药理学意义的结构。 因此一个 系列阿拉伯核苷类似物，特别是 dideaza ara-C 类似物，最有效的抗急性药物之一 白血病，环尿苷和环胞苷的苯类似物，如 与抗病毒剂相关的吲哚C-核苷是-A 通过适当的分子内C-糖基化来制备 取代苯和吲哚衍生物。 拟议的 方法论还提供了一种了解自然内部 C 的简短方法 糖苷，例如岩白菜素和相关化合物，以及 C-糖基黄酮类化合物。 此外，N-苄基化氨基糖 是手性四氢异喹啉的前体，具有 由于其关系，替换模式非常有趣 与衍生自生物胺的四氢异喹啉相比 和某些精神药理学药物。 C-苄基化 相应的N-亚苄基亚氨基糖，预计将是高度 立体选择性，给出一种应该导致一个的中间体 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元的短合成路线 氢异喹啉生物碱。

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.