Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 20, 2023
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Indolizidine 209D (Qiu/He/Zhang), Kopsone (Yokoshima), Quinocarcin (Zheng/Huang), Daphnillonin B (Li), Daphnezomine B (Zhai), Vilmoraconitine (Liu/Qin)

Indolizidine 209D (3), isolated from the neotropical "poison dart" frog, inhibits neuromuscular transmission. Hanyue Qiu, Ling He and Min Zhang of Chongqing University rearranged the cyclopropanol 1, prepared from the corresponding ester by the Kulinkovich reaction, to a ketone that was reduced to the alcohol 2. Further reduction led to 3 (Org. Lett. 2023, 25, 2058. DOI: 10.1021/acs.orglett.3c00406).

Kopsone (6) was isolated from the Malaysian shrub Kopsia profunda. En route to 6, Satoshi Yokoshima of Nagoya University cyclized the unsaturated aldehyde 4 to the tricyclic 5 (Org. Lett. 2023, 25, 2718. DOI: 10.1021/acs.orglett.3c00838).

Quinocarcin (10), isolated from the culture broth of Streptomyces melanovinaceus, showed remarkable antiproliferative activity against lymphocytic leukemia, non-small cell lung cancer, and adenocarcinoma. Jian-Feng Zheng and Pei-Qiang Huang of Xiamen University secured the absolute configuration of 10 by the reduction of the amide 7, followed by Cu-catalyzed dipolar cycloaddition to t-butyl acrylate 8 to give 9 (Angew. Chem. Int. Ed. 2023, 62, e202302832. DOI: 10.1002/anie.202302832).

Daphnillonin B (13) was isolated from the tropical tree Daphniphyllum longeracemosa. Chuang-Chuang Li of the Southern University of Science and Technology constructed the piperidine of 13 by the Ru-catalyzed cyclization of 11 to 12, followed by further reduction (J. Am. Chem. Soc. 2023, 145, 10998. DOI: 10.1021/jacs.3c03755).

Daphnezomine B (16), isolated from the leaves of the East Asian shrub Daphniphyllum humile, showed cytotoxicity toward murine lymphoma L1210 cells. Hongbin Zhai of the Shenzhen Graduate School of Peking University assembled the piperidine ring of 16 by the one-electron reduction and cyclization of the piperitone-derived epoxide 14 to 15 (Angew. Chem. Int. Ed. 2023, 62, e202303402. DOI: 10.1002/anie.202303402).

Vilmoraconitine (19) was isolated from the herb Aconitum vilmorinianum, used in traditional Chinese medicine to treat rheumatism and pains. Xiao-Yu Liu and Yong Qin of the West China School of Pharmacy assembled the key tetracyclic intermediate 18 by the intramolecular Mannich cyclization of the keto aldehyde 17 (J. Am. Chem. Soc. 2023, 145, 3903. DOI: 10.1021/jacs.3c00318).

D. F. Taber, Org. Chem. Highlights 2023, November 20.