Journey to jorumycin Jorumycin is a structurally complex, pentacyclic organic compound produced by a marine mollusk. The success of a similar compound, trabectedin, in treating certain types of cancer has focused attention on exploring jorumycin's pharmaceutical properties. Welin et al. developed a succinct route to synthesizing jorumycin and the closely related jorunnamycin A that deliberately diverges from the putative biosynthetic pathway underlying prior chemical syntheses. This route, which hinges on a carefully optimized asymmetric catalytic hydrogenation, can be easily modified to introduce unnatural structural diversity for functional optimization in further drug discovery research. Science, this issue p. 270 A route to two marine natural products distinct from the biosynthesis enables structural diversification for drug discovery. The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong Gram-positive and Gram-negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet–Spengler reaction, that mimics their biosynthetic pathways. Herein, we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of nonnatural analogs.

中文翻译：

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通过不对称催化实现 (-)-jorunnamycin A 和 (-)-jorumycin 的简明全合成

Jorumycin 之旅 Jorumycin 是一种结构复杂的五环有机化合物，由海洋软体动物产生。类似化合物曲贝替定在治疗某些类型的癌症方面取得的成功使人们的注意力集中在探索乔鲁霉素的药物特性上。韦林等人。开发了一种简洁的途径来合成 jorumycin 和密切相关的 jorunnamycin A，该途径故意偏离先前化学合成的假定生物合成途径。该路线取决于精心优化的不对称催化氢化，可以轻松修改以引入非自然结构多样性，以在进一步的药物发现研究中进行功能优化。科学，这个问题 p。270 两种不同于生物合成的海洋天然产物的途径使药物发现的结构多样化成为可能。双四氢异喹啉 (bis-THIQ) 天然产物除了具有很强的革兰氏阳性和革兰氏阴性抗生素特性外，还因其异常有效的抗癌活性而得到深入研究。这些复杂多环化合物的合成策略在很大程度上依赖于亲电芳香化学，例如模仿其生物合成途径的 Pictet-Spengler 反应。在此，我们报告了两种双 THIQ 天然产物 jorunnamycin A 和 jorumycin 的方法，该方法利用现代过渡金属催化的力量进行三个主要的键形成事件，并以高效率进行（分别为 15 和 16 步） ）。通过打破仿生学，这种策略允许制备更多样化的非天然类似物。