Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 15, 2021
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Drupacine (Kim), Fawcettidine (Yao), Tetraponerine T8 (Nelson/Marsden), Lycoplatyrine A (Sarpong), Alsmaphorazine C (Ding), Halichlorine (Carreira)

Drupacine (4) was isolated from the plum yew Cephalotaxus harringtonia, also the source for the anti-cancer alkaloid homoharringtonine. Sanghee Kim of Seoul National University devised a general route to the Cephalotaxus alkaloids, including 4, based on the N-alkylation of the proline-derived lactone 1 with the bromide 2, followed by DBU-mediated rearrangement to 3 (Angew. Chem. Int. Ed. 2021, 60, 12060. DOI: 10.1002/anie.202101766).

Fawcettidine (7) was isolated from the clubmoss Lycopodium fawcettii of Jamaica. Zhu-Jun Yao of Nanjing University assembled 7 by the reductive cyclization of 5 to the ketone 6 (Org. Lett. 2021, 23, 3578. DOI: 10.1021/acs.orglett.1c00977).

Adam Nelson and Stephen P. Marsden of the University of Leeds devised the efficient cyclization of the protected piperidine 8 to the bicyclic sulfonamide 9. Deprotection with the diamine 10 followed by condensation with the bromoaldehyde 11 led to the alkaloid tetraponerine T8 (12), isolated from the toxin of the Papua New Guinean ant Tetraponera punctulata (Chem. Commun. 2021, 57, 919. DOI: 10.1039/D0CC07625B).

Richmond Sarpong of the University of California, Berkeley used Ir-catalyzed remote functionalization to convert the pyridine 13 to the 5-bromopyridine 14. Coupling with the β-lactam 15 led to the Lycopodium alkaloid lycoplatyrine A (16) (J. Am. Chem. Soc. 2021, 143, 4732. DOI: 10.1021/jacs.1c00457).

Hanfeng Ding of Zhejiang University assembled alsmaphorazine C (19) from the ketone 18, prepared by irradiation of the lactam 17. The absolute configuration of 17 and so of 19 was set by enantioselective hydrogenation of the corresponding ketone (Angew. Chem. Int. Ed. 2021, 60, 10603. DOI: 10.1002/anie.202101752).

Erick M. Carreira of the Eidgenössische Technische Hochschule Zürich used an Ir catalyst to cyclize one enantiomer of the racemic alcohol 20 to a nitrone, that was converted thermally to the tricyclic piperidine 21. The amine 21 was carried on to a known advanced intermediate in the synthesis of halichlorine (22), isolated from the marine sponge Halichondria okadai (Angew. Chem. Int. Ed. 2021, 60, 9913. DOI: 10.1002/anie.202100150).

D. F. Taber, Org. Chem. Highlights 2021, November 15.