Arrays of Stereogenic Centers: The Hajra Synthesis of Podophyllotoxin

Matthew J. Vetticatt of Binghamton University and William D. Wulff of Michigan State University used a VANOL-derived Al catalyst to construct the epoxy amide 3 by the addition of the diazo acetamide 2 to the aldehyde 1 (ACS Catal. 2023, 13, 13117. DOI: 10.1021/acscatal.3c03929). Binju Wang of Xiamen University, Wonwoo Nam of Ewha Womans University and Bin Wang of the University of Jinan effected enantioselective dihydroxylation of the unsaturated ester 4, leading to the diol 5 (J. Am. Chem. Soc. 2023, 145, 27626. DOI: 10.1021/jacs.3c09508). Chen Xu of the Southern University of Science and Technology optimized the aryl ether of the prochiral 6, enabling osmylation to 7 in high ee (ACS Catal. 2023, 13, 9745. DOI: 10.1021/acscatal.3c02488). Géraldine Masson of the Université Paris-Saclay used a BINOL-derived phosphoric acid to prepare 9 by the cycloaddition of a nitrosoarene with the triene 8 (J. Am. Chem. Soc. 2023, 145, 26504. DOI: 10.1021/jacs.3c12015).

Haihui Peng and Guosheng Liu of the Shanghai Institute of Organic Chemistry showed that oxidative carboxylation of the internal alkene 10 led to the ester 11 (Asian J. Org. Chem. 2023, 12, e202300165. DOI: 10.1002/ajoc.202300165). Shin-ichi Hirashima and Tsuyoshi Miura of the Tokyo University of Pharmacy and Life Sciences assembled the nitrile 14 by the thiourea-mediated addition of the lactam 12 to the enone 13 (Asian J. Org. Chem. 2023, 12, e202300082. DOI: 10.1002/ajoc.202300082). Shaolin Zhu of Nanjing University prepared the α-amino amide 17 by addition of the bromoamide 15 to the enamide 16 (Angew. Chem. Int. Ed. 2023, 62, e202311094. DOI: 10.1002/anie.202311094). Arnau Call and Miquel Costas of the Universitat de Girona and Massimo Bietti of the Università "Tor Vergata" effected the oxidative cyclization of the acid 18 to the lactone 19 (J. Am. Chem. Soc. 2023, 145, 18094. DOI: 10.1021/jacs.3c06231).

Hao Song and Yong Qin of Sichuan University effected the enantioselective hydrogenation of the alkene 20 to the lactam 21 (Org. Chem. Front. 2023, 10, 5070. DOI: 10.1039/D3QO01196H). Zhenbo Yuan, Jingwen Zhou and Yijian Rao of Jiangnan University engineered an ene reductase that mediated the photocyclization of the bromide 22 to the ketone 23 (Angew. Chem. Int. Ed. 2023, 62, e202311762. DOI: 10.1002/anie.202311762). Wenwei Lin of the National Taiwan Normal University also used a thiourea catalyst to mediate the assembly of the pyrrolidine 26 by the addition of the azomethine ylide derived from 25 to the Meldrum's acid derivative 24 (Adv. Synth. Catal. 2023, 365, 3603. DOI: 10.1002/adsc.202300609). Zhi-Yong Han and Liu-Zhu Gong of the University of Science and Technology of China prepared the 2,3-diaryl lactone 28 by the addition of CO and benzyl bromide to the α-keto phosphonate 27 (Org. Biomol. Chem. 2023, 21, 7305. DOI: 10.1039/D3OB01267K).

Podophyllotoxin (32), isolated inter alia from the American mayapple Podophyllum peltatum, is a clinically important antiviral and anticancer agent. Saumen Hajra of the Centre of Biomedical Research showed that proline, the simplest of organocatalysts, was sufficient to couple the aldehyde 29 with the aldehyde 30, leading to the lactone 31 in high ee (Org. Biomol. Chem. 2023, 21, 8749. DOI: 10.1039/D3OB01446K).