Antineoplastic Agents. 450. Synthesis of (+)-Pancratistatin from (+)-Narciclasine as Relay^1a

Abstract

(+)-Narciclasine (2) available in quantity from certain Amaryllidaceae species or by total synthesis was employed as a precursor for a 10-step synthetic conversion (3.6% overall yield) to natural (+)-pancratistatin (1a). The key procedures involved epoxidation of natural (+)-narciclasine (2) to epoxide 6, reduction to diol 8, and formation of cyclic sulfate 12 and its ring opening with cesium benzoate followed by saponification of the benzoate to afford (+)-pancratistatin (1a).

Total Syntheses of Pancratistatin. A Review

“…Pettit and coworkers developed a new route to pancratistatin 85 using its more naturally abundant congener narciclasine as the starting material. The synthesis commenced with the protection of the C3,C4-vicinal diol as an acetonide in 97% yield (Scheme 31).…”

Chemistry and Synthesis of Highly Oxygenated Alkaloids from Amaryllidaceae: Lycoricidine, Narciclasine, Pancratistatin and Analogs

“…To circumvent the scarcity of pancratistatin in plants, a route to10b-Rhydroxy-pancratistatin from narciclasine was devised providing analogs for biological evaluation [53,47]. A 10-step conversion of narciclasine to pancratistatin has been also achieved (vide infra) [54,55].…”

“…protection was used and functionalization of the double bond of 262 was carried out by stereoselective epoxidation using mCPBA [54]. Reduction of the epoxide 263 provided a mixture of four compounds among which the desired alcohol 264, its 10a-epimer, and 10b-R-hydroxy-isonarciclasine (not shown) were isolated in a 1.5:1.5:1 ratio.…”

Synthesis of Amaryllidaceae Constituents - An Update

“…36 Acetylation of the 3,4-acetonide of narciclasine at C-3 and C-7 was followed by oxidation of the olefin to afford epoxide 40 (Scheme 8). Hydrogenation of this material in the presence of 10% palladium on carbon and subsequent saponification yielded in a mixture of four compounds, one of them, the desired diol 41, in 28% yield.…”