Today, more than 100 Food and Drug Administration-approved steroidal agents are prescribed daily for indications including heart failure, inflammation, pain and cancer. While triumphs in organic chemistry have enabled the establishment and sustained growth of the steroid pharmaceutical industry, the production of highly functionalized synthetic steroids of varying substitution and stereochemistry remains challenging, despite the numerous reports of elegant strategies for their de novo synthesis. Here, we describe an advance in chemical synthesis that has established an enantiospecific means to access novel steroids with unprecedented facility and flexibility through the sequential use of two powerful ring-forming reactions: a modern metallacycle-mediated annulative cross-coupling and a new acid-catalysed vinylcyclopropane rearrangement cascade. In addition to accessing synthetic steroids of either enantiomeric series, these steroidal products have been selectively functionalized within each of the four carbocyclic rings, a synthetic ent-steroid has been prepared on a multigram scale, the enantiomer of a selective oestrogen has been synthesized, and a novel ent-steroid with growth inhibitory properties in three cancer cell lines has been discovered.

中文翻译：

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合成NAT-或ent-从环氧氯丙烷最初的5个化学步骤类固醇

如今，每天都会开出100多种获得美国食品药品监督管理局（FDA）批准的类固醇药物处方，用于包括心力衰竭，炎症，疼痛和癌症的适应症。尽管有机化学的成功推动了类固醇制药行业的建立和持续增长，尽管有许多报道称从头开始采用了优雅的策略，但生产具有高度不同取代度和立体化学的功能化合成类固醇仍具有挑战性合成。在这里，我们描述了化学合成技术的进步，该技术已经建立了一种对映体特异性的方法，可以通过顺序使用两种强大的成环反应来获得具有空前便利性和灵活性的新型类固醇：现代金属环磷酰胺介导的环状交叉偶联和新的酸催化的乙烯基环丙烷重排级联反应。除了访问任一对映体一系列合成的类固醇，甾体类，这些产品已经选择性内四个碳环的官能化，合成耳鼻喉科-steroid已经在多克规模制备，选择性雌激素的对映体已被合成，并且一种新颖的耳鼻喉科在三个癌症细胞系的生长抑制性质-steroid已经发现。