Faculty of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland.
Org Biomol Chem. 2016 Jan 14;14(2):460-469. doi: 10.1039/c5ob01844g.
We have developed a strategy for the stereoselective synthesis of cyclolignans related to podophyllotoxin and its derivatives. The crucial step of the synthesis is the photocyclization of a chiral atropoisomeric 1,2-bisbenzylidenesuccinate amide ester, which can be prepared from suitable aromatic aldehydes, diethyl succinate and l-prolinol. The photocyclization was found to be more efficient when irradiation was performed in a home-built continuous flow photochemical reactor. The in-flow irradiation also allowed us to perform the reaction on a multigram scale. The chiral auxiliary was removed by reductive cleavage with the Schwartz's reagent to give the cytotoxic 1R,2R-cis-podophyllic aldehyde, which in turn could be easily reduced to the corresponding alcohol, completing the formal synthesis of (-)-podophyllotoxin.
我们开发了一种与鬼臼毒素及其衍生物相关的环木脂素的立体选择性合成策略。合成的关键步骤是手性的非对映异构 1,2-双亚苄基琥珀酸酰胺酯的光环化，它可以从合适的芳香醛、琥珀酸二乙酯和 L-脯氨酸制备得到。当在自制的连续流动光化学反应器中进行照射时，光环化反应的效率更高。在流中照射还允许我们在多克规模上进行反应。通过用施瓦茨试剂进行还原裂解除去手性辅助剂，得到细胞毒性的 1R,2R-顺式鬼臼基醛，它可以很容易地还原成相应的醇，从而完成了（-）-鬼臼毒素的形式合成。
