Alkaloid Synthesis: Allokainic acid (Tilve), Preussin (Ryu), Toussaintine C (Hayakawa), Powelline (Tang), Arborduridine (Ma), Securine A (Herzon)

The kainic acids, exemplified by allokainic acid (5), isolated from the tropical seaweed Digenea simplex, have become important tools for neurological investigation. Santosh G. Tilve of Goa University used the Hayashi-Jørgensen amine to mediate the coupling of the aldehyde 1 with ethyl glyoxylate 2, leading, after reductive amination with the amine 3, to the lactam 4, a precursor to 5 (Org. Biomol. Chem. 2023, 21, 5469. DOI: 10.1039/D3OB00707C).

Preussin (8) was isolated initially from Aspergillus ochraceus, and from Preussia sp. shortly thereafter. Jae-Sang Ryu of Ewha Womens University prepared 8 by way of the Mitsunobu cyclization of the sulfamidate 6 to the bicyclic 7 (J. Org. Chem. 2023, 88, 9902. DOI: 10.1021/acs.joc.3c00670).

Toussaintine C (11) was isolated from the leaves of Toussaintia orientalis, a flowering plant of Tanzania and Kenya. Ichiro Hayakawa of Nihon University optimized the oxidation of the tyramine-derived amide 9, then cyclized the resulting cyclohexadienone 10 to 11 (J. Org. Chem. 2024, 89, 8931. DOI: 10.1021/acs.joc.4c00818).

Powelline (14) was isolated from the Cape lilly Crinum x powellii. Yefeng Tang of Tsinghua University achieved high enantioselectivity in the reductive cyclization of 12 to 13, that was carried on to 14 (J. Am. Chem. Soc. 2024, 146, 14136. DOI: 10.1021/jacs.4c02755).

Arboduridine (17) was isolated from the south China tree Kopsia arborea Blume. In the course of a synthesis of 17, Zhiqiang Ma of the South China University of Technology devised the cyclization of the amino ketone 15 to the piperidine 16 (Angew. Chem. Int. Ed. 2024, 63, e202316016. DOI: 10.1002/anie.202316016).

Securine A (20) was isolated from the subtidal bryzoan Securiflustra securifrons of the British Isles. Seth B. Herzon of Yale University cyclized the aryl azide 18 to the aminal 19. Deprotection with BCl₃ also led to ring opening, to give 20. Deprotection prior to cyclization led to the deprotected form of 19, also a natural product, securamine A (Science 2024, 383, 849. DOI: 10.1126/science.adl6).