Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 15, 2024
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Hinckdentine A (Rawal), Isolycoricidine (Canesi), Normacusine B (Qi), Silicine (Ishikawa), Cephalocyclidin A (Zhang/Tu), Alstolucine B (Lan/Zhang)

Hinckdentine A (3) was isolated from the bryozoan Hincksinoflustra denticulata collected on the eastern coast of Tasmania. En route to 3, Viresh H. Rawal of the University of Chicago observed clean stereochemical transfer in the Meerwein-Eschenmoser-Claisen rearrangement of the secondary alcohol 1 to the amide 2 (J. Am. Chem. Soc. 2023, 145, 14831. DOI: 10.1021/jacs.3c03611).

The Amaryllidacae alkaloids, including isolycoricidine (6), show significant anti-viral activity. Sylvain Canesi of the Université de Québec à Montréal assembled 6 via the enantioselective Heck cyclization of 4 to 5 (Adv. Synth. Catal. 2023, 365, 3521. DOI: 10.1002/adsc.202300801).

Normacusine B (9), also known as vellosiminol, is a hypotensive alkaloid isolated from the root of Strychnos atlantica an evergreen of Brazil. Xiangbing Qi assembled the skeleton of 9 by the aza-Achmatowicz reaarrangement of the furan 7 to the enone 8 (Angew. Chem. Int. Ed. 2023, 62, e202304435. DOI: 10.1002/anie.202304435).

Silicine (13) was isolated from the tropical devil pepper Rauwolfia discolor. Hayato Ishikawa of Chiba University used a Hayashi-Jørgensen catalyst to guide the absolute configuration of the addition of 11 to 10, leading to 12 in high ee (Org. Lett. 2023, 25, 7601. DOI: 10.1021/acs.orglett.3c02590).

Cephalocyclidin A (16) is a cytotoxic alkaloid isolated from the fruits of the Japanese plum yew Cephalotaxus harringtonia var. nana. Xiao-Ming Zhang and Yong-Qiang Tu of Lanzhou University achieved high diastereoselectivity and enantioselectivity in the cyclization of the α-keto amide 14 to the tetracyclic precursor 15 (J. Am. Chem. Soc. 2023, 145, 26550. DOI: 10.1021/jacs.3c11178).

Alstolucine B (19) was isolated from the Siamese balsa Astonia spatulata. Yu Lan and Min Zhang of Chongqing University set the absolute configuration of 19 by the enantioselective cyclization of the prochiral cyclohexanone 17 to the bicyclic ketone 18 (Nature Chem. 2023, 15, 1074. DOI: 10.1038/s41557-023-01264-4).

D. F. Taber, Org. Chem. Highlights 2024, April 15.