Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 18, 2022
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Impatien A (Watson), cis-195J (Schneider), Galanthamine (Zhao), Stemoamide (Tang), Lythranidine (Sherburn), Aspidospermine (Liu)

Impatien A (3) was isolated from the Corydalis impatien, a flower of south China that is an important component in traditional Chinese medicine. Donald A. Watson of the University of Delaware established the spiro ring fusion of 3 by the Pd-catalyzed cyclization of the phenoxy amide 1 to the lactam 2 (Org. Lett. 2021, 23, 7285. DOI: 10.1021/acs.orglett.1c02767).

The alkaloid cis-195J (6a or 6b) was isolated from the skin extract of the neotropical dendrobatid frog Mantella betsileo. Christoph Schneider of the Universitšt Leipzig individually prepared 6a and 6b from the trisubstituted piperidine 5, assembled by the cyclization of the alkyne 4 followed by reduction. Biosynthetic considerations suggest that the natural product is 6b, but confirmation of this will wait on comparison with the natural alkaloid (J. Org. Chem. 2021, 86, 11960. DOI: 10.1021/acs.joc.1c01346).

Galanthamine (9), isolated from the common daffodil, has found widespread application in the treatment of dementia. Yu-Ming Zhao of Shaanxi Normal University developed a route to 9 by way of the lactam 8, prepared by the acid-mediated rearrangement of the hemiaminal 7, followed by reduction (Org. Lett. 2021, 23, 9659. DOI: 10.1021/acs.orglett.1c03943).

Stemoamide (11) was isolated from Stemona tuberosa, a flowering plant native to China, India, southeast Asia, and New Guinea. Yefeng Tang of Tsinghua University achieved high diastereoselectivity in the reduction of the imine derived from 10, leading directly, after spontaneous lactam formation, to 11 (Angew. Chem. Int. Ed. 2021, 60, 14545. DOI: 10.1002/anie.202102614).

The macrocyclic alkaloid lythranidine (14) was isolated from the Japanese perennial Lythrum anceps Makino. Michael S. Sherburn of Australian National University carried the diester 12 on to the 17-membered ring dienone, condensed that with benzylamine, then reduced the diketone so produced to the diol 13. Selective deprotection then completed the synthesis of 14 (Angew. Chem. Int. Ed. 2021, 60, 18561. DOI: 10.1002/anie.202107524).

Aspidospermine (17), isolated from the tree Aspidosperma of tropical South America, has adrenergic blocking activity. Yongxiang Liu of Shenyang Pharmaceutical University assembled the pentacyclic ketone 16 by the Ag-mediated cyclization of the iodide 15, followed by reduction (Org. Lett. 2021, 23, 6471. DOI: 10.1021/acs.orglett.1c02287).

D. F. Taber, Org. Chem. Highlights 2022, April 18.