A Photoflow Reactor for the Continuous Photoredox-Mediated Synthesis of C-Glycoamino Acids and C-Glycolipids
A Photoflow Reactor for the Continuous Photoredox-Mediated Synthesis of C-Glycoamino Acids and C-Glycolipids
复制标题
DOI：
10.1002/anie.201200593
复制
发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Gagne, Michel R.
中科院分区：
文献类型：
--
作者：
Andrews, R. Stephen;Becker, Jennifer J.;Gagne, Michel R.
糖复合物是具有多种功能的重要生物化合物。例如，糖蛋白参与细胞间识别事件，例如免疫反应，并且与糖脂一起帮助形成哺乳动物细胞表面。 [1]这些见解与其在疫苗治疗中的潜力相结合[2]继续推动研究，以表征糖复合物在生物过程中的作用。糖复合物的一个共同特征是 O-糖苷键的代谢不稳定性，[3] 它刺激了 C-糖苷等排体的发展 [4]，以克服这种水解不稳定性，从而延长生物利用度。尽管付出了巨大的努力，仍然需要改进的 C-糖苷合成方法。 [5]为此，我们报道了通过镍催化 [6, 7] 和光氧化还原过程合成 C-糖苷的温和方法。 [8]后一种方法作为一种利用光化学能产生自由基的温和方法而受到了极大的关注。 [9]我们在此报告了一种高产且可扩展的 C-糖肽和 C-糖脂方法，该方法利用连续（流动）光氧化还原过程。[10, 11]先前报道的 C-糖肽合成包括手性烯烃的交叉复分解，[12] Ramberg-Bäcklund 烯化/氢化序列，[13] 添加手性碳 亲核试剂转化为糖基亲电试剂，[14]以及醛的有机催化酰胺化。[15]虽然有效，但这些方法需要多个合成步骤、使用昂贵或有毒的试剂、苛刻的反应条件（强酸或碱）或使用手性起始材料（手性助剂或氨基酸衍生的）。作为一种更有效的替代方案，我们设想使用我们最近报道的可见光光氧化还原介导的方法从商业来源一步获得醛 1，[8a] 可以作为 C-糖复合物模拟物的不同合成的关键中间体（方案 1）。
Glycoconjugates are essential biological compounds having various functions. For example, glycoproteins are involved in intercellular recognition events, such as immune response, and along with glycolipids they help to form mammalian cell surfaces.[1] These insights combined with their potential in vaccine therapeutics [2] continue to drive investigations to characterize the role of glycoconjugates in biological processes. A common feature of glycoconjugates is the metabolic instability of the O-glycosidic linkage,[3] which has stimulated the development of C-glycoside isosteres [4] to overcome this hydrolytic instability and thus extend bioavailability. Despite extensive efforts, improved methods of C-glycoside synthesis are still in demand.[5] To this end we have reported mild methods of C-glycoside synthesis through nickel-catalyzed [6, 7] and photoredox processes.[8] The latter approach has received significant interest as a mild method of generating radicals using photochemical energy.[9] We report herein a highyielding and scalable approach to C-glycopeptides and C-glycolipids which utilizes a continuous (flow) photoredox process.[10, 11]Previously reported syntheses of C-glycopeptides include the cross-metathesis of chiral alkenes,[12] Ramberg–Bäcklund olefination/hydrogenation seuqences,[13] addition of chiral carbon nucleophiles to glycosyl electrophiles,[14] and organocatalytic amidation of aldehydes.[15] While effective, these methods require multiple synthetic steps, use expensive or toxic reagents, harsh reaction conditions (strong acid or base), or the use of chiral starting materials (chiral auxiliaries or amino-acid-derived). As a more efficient alternative, we envisioned that aldehyde 1, accessible in one step from commercial sources using our recently reported visible-light photoredox-mediated methodology,[8a] could function as a key intermediate for the divergent synthesis of C-glycoconjugate mimics (Scheme 1).