Total Synthesis of (−)-Cardiopetaline

Abstract

The total synthesis of (-)-cardiopetaline, an aconitine-type natural product, has been accomplished. Our synthesis involved a Wagner-Meerwein rearrangement of a sulfonyloxirane that enabled, in a single step, the construction of the bicyclo[3.2.1] system in the aconitine skeleton and effective introduction of oxygen functional groups at the appropriate positions.

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

“…As it turned out, the sulfides derived from aldehydes 7-9 and 11 failed to undergo a rearrangement ( [13][14][15][16][17][18]. This sulfur atom phosphorus-to-carbon migration in phosphine sulfides has previously been mentioned only once in the literature [59].…”

“…Among all organic reactions, rearrangements are an exciting class of transformations where unusual or even unexpected products can be obtained. Many rearrangements are of practical use in synthetic organic chemistry, including Beckmann [1][2][3][4], Claisen [5][6][7][8], pinacol [9][10][11][12], Wagner-Meerwein [13][14][15][16], Curtius [17][18][19][20], Hofmann [21][22][23][24], Overmann [25][26][27][28] rearrangements, and many others. In organophosphorus chemistry, rearrangements are less developed transformations, however, some examples can be found in the literature (Scheme 1).…”

Synthesis of Atisine, Ajaconine, Denudatine, and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach

“…Owing to their architectural complexity and diversity, the chemical synthesis of diterpenoid alkaloids has attracted considerable attention . Whereas most synthetic endeavors targeted a specific structural type, the groups of Wiesner,, Sarpong, and Fukuyama completed the total synthesis of aconitine‐type diterpenoid alkaloids by critical Wagner–Meerwein‐type rearrangement reactions from the denudatine skeletons, as guided by the biosynthetic hypothesis. Furthermore, Baran and co‐workers reported an elegant approach to a hetidine core structure through a tandem condensation/azomethine ylide isomerization/Mannich cyclization sequence via a putative atisine intermediate .…”

Reductive cyclization strategy for construction of the highly oxygenated CD ring system of aconitine

“…These structural and biological properties have attracted significant attention from synthetic chemists over the past decades, 2,3 which has resulted in the successful total syntheses of talatisamine (2), 4 chasmanine (3), 5 13-deoxydelphonine (4), 5 liljestrandinine (5), 6 and cardiopetaline (6). 7 However, these C 19 -diterpenoid alkaloids have a relatively simple D ring, and chemical syntheses of natural products that have a more oxygenated D ring, such as aconitine (1), remain a great challenge. In our program toward the total synthesis of 1, we decided to explore an efficient methodology for constructing the D ring with all the oxygen functionalities installed stereoselectively.…”