INTRAMOLECULAR C-GLYCOSIDATION OF SUBSTITUTED SUGARS

一种立体定向合成C-C-的新方法 提出了糖苷类化合物的新概念。此方法基于 含潜伏期取代基的初步附着 碳的亲核功能是一种羟基功能 环糖衍生物，然后产生一种碳- 该基团和该基团的反常中心之间的碳键 糖。因此，O-苯基化糖、N-苯基化糖和O-苯基糖 应该导致“内部”C-糖苷(等色质， 四氢异喹啉和2，3-二氢苯并呋喃。)哪一个 可以裂解成C-糖基化的苯衍生物或进一步 精制的(例如，四氢异喹啉生物碱)。 C-亲核剂的一步转移可以用以下方法实现 一种双官能硅基衍生物，作为糖的临时键- 羟基功能：如O-芳氧基硅基，以及O-芳基和O- 烯丙基-二甲基硅基碳水化合物衍生物有望 同时进行分子内C-糖苷化反应 在使用Lewis处理时辅助连接的切割 酸，从而提供了一种高效和通用的方法 立体特异的C-糖苷化。 这一方法学将被用于合成一些 具有生物和药理意义的结构。因此，一个 一系列阿拉伯核苷类似物，特别是二氮杂 Ara-C的类似物，抗急性胰腺炎最有效的药物之一 白血病，环胞苷和环胞苷的苯类类似物，AS 与抗病毒药物相关的吲哚C-核苷是-A意愿 适当地通过分子内C-糖基化反应制备 取代苯和吲哚衍生物。建议数 方法论还提供了一种简单的方法来实现自然的内部C- 如岩白菜素和相关化合物等糖苷，以及 C-糖基黄酮类化合物。此外，N-苄基氨基糖 是手性四氢异喹啉的前体，它具有 非常有趣的替换模式，因为它的关系 对生物胺衍生的四氢异喹啉的影响 以及某些精神药理药物。C-苄基化反应 相应的N-亚苄亚胺糖，预计会很高 立体选择性，给出一种中间体，它应该是一种中间体 步骤，通过“双分子内C-芳基化”过程，得到 异丙肾上腺素生物碱的骨架。这些反应提供了一种 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。

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.