Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 17, 2023
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Tabertinggine (She), Kopisinine (Ruijter), Sieboldine A (Yao), Rhazinicine (Miranda), Brevianamide A (Gagosz), Daphlongamine E (Xu)

Tabertinggine (4) was isolated from the Mayasian shrub Tabernaemontana corymbosa, the dwarf pinwheel. Xuegong She of Lanzhou University assembled the key tetracyclic intermediate 3 by the BINOL-derived phosphoric acid mediated Pictet-Spenger combination of tryptamine (1) with the α-keto diester 2 (Eur. J. Org. Chem. 2022, e202200088. DOI: 10.1002/ejoc.202200088).

Kopisinine (7), isolated from the Southeast Asian tree Kopsia longiflora, shows strong antitussive properties. En route to 7, Eelco Ruijter of the Vrije Universiteit Amsterdam effected the cyclization of the chloroacetamide 5 to the pentacyclic 6 (Angew. Chem. Int. Ed. 2022, e202210592. DOI: 10.1002/anie.202210592).

Sieboldine A (10), isolated from the club moss Lycopodium sieboldii, is an inhibitor of acetylcholine esterase. Zhu-Jun Yao of Nanjing University prepared the amine 9 by acid-mediated cyclization of the hemiacetal 8 (Org. Lett. 2022, 24, 7517. DOI: 10.1021/acs.orglett.2c02737).

Rhazinicine (13), isolated from Kopsia dasyrachis, a tree of Sabah, Borneo, showed selective cytotoxicity in vitro. Following the precedent of Trauner (Pd-Mediated Arylation of Aromatic and Heteroaromatic Rings 2006, March 27), Luis D. Miranda of the Universidad Nacional Autónoma de México assembled the macrocyclic lactam of 13 by the Pd-mediated cyclization of 11 to 12 (Org. Lett. 2022, 24, 8093. DOI: 10.1021/acs.orglett.2c02446).

Brevianamide (17), isolated from the fungus Penicillium brevicompactum, demonstrated potent antifeedant activity. Fabien Gagosz of the University of Ottawa assembled the amine 16 by Au-catalysed combination of the alkyne azide 14 with prenyl alcohol 16, and showed that on hydrolysis it spontaneously cyclized to 17 (Org. Lett. 2022, 24, 7200. DOI: 10.1021/acs.orglett.2c02971).

Daphlongamine E (20) was isolated from the Chinese evergreen tree Daphniphyllum longeracemosum. In a continuation of their studies of the Daphniphyllum alkaloids, Jing Xu of the Southern University of Science and Technology described the Heck cyclization of the alkenyl bromide 18 to the tetracyclic lactam 19 (J. Am. Chem. Soc. 2022, 144, 16042, DOI: 10.1021/jacs.2c05957; Org. Lett. 2022, 24, 7416, DOI: 10.1021/acs.orglett.2c02988).

D. F. Taber, Org. Chem. Highlights 2023, April 17.