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

阿奎阿霉素是一种糖基和芳香族发色团杂化结构的抗生素，为了探索碳水化合物合成和芳香族化合物合成的新方向，我们进行了阿卡霉素的合成研究。利用我们首次开发的O-→C-糖苷重排反应和[2+2]环加成反应，成功地合成了AB环片段，即含有C-橄榄糖苷的3-(苯磺酰基)苯酞。以脂肪酶促进的环己烷-1，2，3-三醇衍生物的不对称脱对称反应为关键步骤，合成了具有高度氧官能团化的手性环己烯环状碎片。这两个片段通过Hauser方法缩合，得到具有C-橄榄苷部分的高度取代的1-蒽酮衍生物。目标分子的C(1)羰基与侧链上的醛部分通过片呐醇偶联反应形成目标分子的四环骨架，最终通过官能团互换反应完成了首次全合成。通过进一步的详细研究，最终缩短和修正了合成路线，使每个片断可以进行多个基团的合成。为了应用于合成具有生理价值的类似物，我们还研究了开发新的有效的氨基糖C-糖苷化的促进剂。另外一个重要的发现是，三氟化钪有效地促进了氨基糖衍生物的芳基-C-糖苷化反应，为合成具有生理价值的类似物打开了机会。

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.