Department of Chemistry and Key Laboratory of Chemical Biology of Fujian Province, iChEM, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao 266000, China.
J Am Chem Soc. 2022 May 25;144(20):8938-8944. doi: 10.1021/jacs.2c03872. Epub 2022 May 16.
A concise and divergent synthesis of the polychlorinated marine steroids clionastatin A and B from inexpensive testosterone has been achieved through a unique two-stage chlorination-oxidation strategy. Key features of the two-stage synthesis include (1) conformationally controlled, highly stereoselective dichlorination at C1 and C2 and C4-OH-directed C19 oxygenation followed by a challenging neopentyl chlorination to install three chlorine atoms; (2) desaturation through one-pot photochemical dibromination-reductive debromination and anti-Markovnikov olefin oxidation by photoredox-metal dual catalysis to enhance the oxidation level of the backbone; and (3) Wharton transposition to furnish the D-ring enone. This synthesis proved that the introduction of the C19 chloride in the early stage of the synthesis secured the stability of the backbone against susceptibility to aromatization during the oxidation stage.
已通过独特的两段式氯化-氧化策略，从廉价的睾丸酮简洁且发散地合成了海洋多氯化甾族化合物 Clionastatin A 和 B。两段式合成的关键特点包括：（1）在 C1 和 C2 以及 C4-OH 导向的 C19 氧原子化作用下，通过构象控制的高立体选择性二氯化作用，随后进行具有挑战性的新戊基氯化作用，以安装三个氯原子；（2）通过一锅光化学二溴化-还原脱溴和光还原-金属双催化反马氏规则烯烃氧化作用进行去饱和作用，以提高骨架的氧化水平；以及（3）通过 Wharton 移位生成 D 环烯酮。该合成证明了在合成的早期阶段引入 C19 氯原子可确保骨架的稳定性，使其在氧化阶段不易发生芳香化。
