Total Synthesis, Relay Synthesis, and Structural Confirmation of the C18-Norditerpenoid Alkaloid Neofinaconitine

Abstract

The first total synthesis of the C18-norditerpenoid aconitine alkaloid neofinaconitine and relay syntheses of neofinaconitine and 9-deoxylappaconitine from condelphine are reported. A modular, convergent synthetic approach involves initial Diels–Alder cycloaddition between two unstable components, cyclopropene 10 and cyclopentadiene 11. A second Diels–Alder reaction features the first use of an azepinone dienophile 8, with high diastereofacial selectivity achieved via rational design of the siloxydiene component 36 with a sterically-demanding bromine substituent. Subsequent Mannich-type N-acyliminium and radical cyclizations provide the complete hexacyclic skeleton 33 of the aconitine alkaloids. Key endgame transformations include installation of the C8-hydroxyl group via conjugate addition of water to a putative strained bridghead enone intermediate 45, and one-carbon oxidative truncation of the C4 sidechain to afford racemic neofinaconitine. Complete structural confirmation was provided by a concise relay synthesis of (+)-neofinaconitine and (+)-9-deoxylappaconitine from condelphine, with X-ray crystallographic analysis of the former clarifying the NMR spectral discrepancy between neofinaconitine and delphicrispuline, which were previously assigned identical structures.

Gold‐Catalyzed Cycloisomerizations of Functionalyzed Cyclopropyl Alkynes: the Cases of Carboxamides and Alcohols

“…[15] In all these transformations, the combination IPrAuCl/AgOTs proved to be the best catalyst system. [22] Interestingly, the gold-catalyzed synthesis of azepinone derivatives has some precedents, for instance, in the preparation of pyrroloazepinones [23] and azepino- [c,d]indolones. [17] At this point it is worth to note that the azepin-2one skeleton is present in both natural and synthetic products displaying useful biological and pharmaco-logical activities, such as natural and synthetic ceratamines 9-11 (antimicotic and microtubule-stabilizing properties), [18] synthetic compound 12 (inhibitor of gsecretase), [19] zatebradine 13 (specific bradycardic agent), [20] or allsterpaullone 14 (promising candidate for therapeutic treatment of type-1 diabetes) [21] (Figure 2).…”

Research Progress on the Synthesis and Application of Cyclopentadiene Derivatives

“…图式 11 1,3-环戊二烯与单线态氧气的反应 Scheme 11 Reaction of 1,3-cyclopentadiene with singlet oxygen 环戊二烯的 Diels-Alder 反应的高反应活性使其在 有机合成 [69] 、生物分子固定化、热敏聚合物和功能性材 料等方面具有广泛的应用 [70,71] . 2015 年, Levandowski…”

Total Synthesis of Talatisamine

“…[6,7] These strategies led to creative solutions enabling the total syntheses of seven C 18and C 19 -diterpenoid alkaloids with various numbers of oxygen functionalities (Figure 1). These include the syntheses of 1 (5 oxygen functionalities,4 3s teps,l ongest linear sequence), chasmanine (6 oxygen functionalities,5 6s teps), and 13desoxydelphonine (6 oxygen functionalities,5 7s teps) by the Wiesner group in the 1970s, [8] neofinaconitine (5 oxygen functionalities,3 4s teps) by the Gin group in 2013, [9] weisaconitine D( 4o xygen functionalities,3 3s teps) and liljestrandinine (4 oxygen functionalities,3 1s teps) by the 19 -diterpenoid alkaloids. X-ray structure of 1 was taken from ref.…”