Synthetic Study of Antibiotic Aquayamycin, Biologically Active Sugar-Aromatic Hybrid

对一种具有糖基和芳香发色团杂合结构的抗生素阿卡霉素进行了合成研究，旨在探索碳水化合物合成和芳香合成的新方向。在项目的早期阶段，我们专注于开拓阿卡霉素的第一代途径。我们最初开发的O→c -糖苷重排和苯和烯基硅基缩醛的[2+2]环加成，成功地合成了AB环片段，即含有c -橄榄苷的3-（苯磺酰基）酞。以脂肪酶促进环己烷-1,2,3-三醇衍生物的不对称脱对称为关键步骤，合成了高氧官能化手性环己烯CD环片段。这两个片段通过Hauser的方法浓缩得到具有c -橄榄苷部分的高取代的1-蒽酮衍生物。该蒽酮的C(1)羰基与侧链上的醛段之间通过蒎醇偶联环化，形成了靶分子的雕刻四环框架，最终官能团相互转换，完成了阿卡霉素的第一次全合成。进一步的详细研究最终缩短和修改了合成路线，使每个片段的合成都是多克合成。为了应用于生理上有用的类似物的合成，我们还研究了开发新的高效的氨基糖c -糖苷化启动子。另一个重要的发现是三氟化钪有效地促进氨基糖衍生物的芳基c -糖苷化，为合成生理上有用的类似物提供了机会。

Synthetic study of aquayamycin, an antibiotic which exhibits the hybid structure composed of sugar moiety and aromatic chromophore, was executed with the aim at exploring new direction of carbohydrate synthesis and aromatic synthesis.In the early stage of the program, we focused on pioneering the first generation route to aquayamycin. The O→C-glycoside rearrangement and the [2+2] cycloaddition of benzyne and ketene silyl acetal, both of which were originally developed by us, were successfully applied for synthesizing the AB ring fragment, i.e. a 3-(phenylsulfonyl)phthalide possessing the C-olivoside. The CD ring fragment, a highly oxygen-functionalized chiral cyclohexene, was synthesized in an enantiomerically pure form via the lipase-promoted asymmetric desymmetrization of cyclohexane-1,2,3-triol derivative as a key step. These two fragments were condensed by the Hauser's method to give the highly substituted 1-anthrone derivative possessing the C-olivoside moiety. Cyclization by pinacol coupling between the C(1) carbonyl of this anthrone and the aldehyde moiety on the side chain furnished the carved tetracyclic framework of the target molecule, and final functional group interconversions led to the accomplishment of the first total synthesis of aquayamycin.Further detailed studies ultimately shortened and revised the synthetic routes so as to render a multi-gram synthesis of each fragment.For the purpose of application to the synthesis of physiologically useful analogue, we also examined to develop new efficient promoter of C-glycosidation of amino sugar.Another significant finding was that scandium(III) triflate efficiently promotes aryl C-glycosidation of amino sugar derivatives, opening an opportunity of synthesizing physiologically useful analogues.