Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 20, 2020
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Lentiginosine (Repo/Samec), (+)-Quinine (Ishikawa), Lasubine II (Pansare), Naucleofficine I (Tu), Vindorosine (Ohno), Taberdivarine H (Poupon/Vincent/Evanno)

Lentiginosine (3), isolated from the California freckled milk vetch Astragalus lentiginosus, is a nanomolar inhibitor of Hsp90 ATPase. Timo Repo of the University of Helsinki and Joseph S. M. Samec of Stockholm University showed that catalytic Fe(OTf)3 cyclized 1 to the pyrrolidine 2 with clean inversion of absolute configuration (Nature Commun. 2019, 10, 3826. DOI: 10.1038/s41467-019-11838-x).

Hayato Ishikawa of Kumamoto University found that the Hayashi catalyst effectively mediated the addition of 5 to 4, leading to 6. This enabled the synthesis of 7, the unnatural enantiomer of quinine (Chem. Sci. 2019, 10, 9433. DOI: 10.1039/C9SC03879E).

Lasubine II (11) was isolated from the crepe myrtle Lagerstroemia subcostata Koehne. Sunil V. Pansare of Memorial University established that proline was a useful organocatalyst for the reaction of the imine trimer 9 with 8, leading to 10 (Org. Lett. 2019, 21, 5524. DOI: 10.1021/acs.orglett.9b01840).

Naucleoofficine I is a cytotoxic alkaloid isolated from the southeast Asian tree Nauclea officinalis. Yong-Qiang Tu of Lanzhou University developed a bifunctional proline-derived catalyst for the addition of acetaldehyde to 12, leading, after acylation with 13 and condensation with the Wittig reagent 14, to the aldehyde 15 (Nature Commun. 2019, 10, 3394. DOI: 10.1038/s41467-019-11382-8).

Vindorosine (19), isolated from the Madagascar periwinkle Catharanthus roseus, constitutes half of the clinically important anti-cancer agents vinblastine and vincristine. En route to 19, Hiroaki Ohno of Kyoto University used a gold catalyst to cyclize 17 to 18 (J. Org. Chem. 2019, 84, 9358. DOI: 10.1021/acs.joc.9b01149).

Taberdivarine H (22) is a cytotoxic alkaloid isolated from the aerial parts of the southern Chinese shrub Tabernaemontana bovina. Erwan Poupon, Guillaume Vincent and Laurent Evanno of the Université Paris-Saclay developed the oxidative cyclization that converted 20 to 21 (Angew. Chem. Int. Ed. 2019, 58, 9861. DOI: 10.1002/anie.201905227).

D. F. Taber, Org. Chem. Highlights 2020, April 20.