The First Total Synthesis of Topsentolide B₃

Abstract

The first total synthesis of the cytotoxic oxylipin Topsentolide B 3 has been accomplished in 15 steps with an overall yield of 24 %. Starting with readily available cis-butene diol as a synthon, the synthesis involved Marouka allylation and Sharpless hydroxylation for the construction of three asymmetric centers. The nine-membered lactone ring was built

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

“…By contrast, G2 catalysts gave better results in the formation of functionalized nonanolactones [213] and in the first total synthesis of topsentolide B3 166. In this case, the formation of the nine-membered ring was accomplished in 78% yield in the presence of G2 (10 mol%) (Scheme 55) [222]. It is worth pointing out that the internal double bonds in the ester substrate 165 remained inert under metathetic Scheme 53 Synthesis of the core structure of eleutherobin and sarcodictyns by ROM-RCM reactions conditions and that the hydroxyl functions may have acted as anchoring groups to the metal center thus assisting the ring-closure process with respect to CM.…”

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

“…[117,119] However, the allylation of a,b-unsaturated carbonyl compounds has been elegantly employed in various total syntheses, including the synthesis of papulacandin D (Scheme 38), [120,121] topsentolide B 3 [122] (Scheme 39), and the C4-C24 fragment of macrolactin A (Scheme 40). [117,119] However, the allylation of a,b-unsaturated carbonyl compounds has been elegantly employed in various total syntheses, including the synthesis of papulacandin D (Scheme 38), [120,121] topsentolide B 3 [122] (Scheme 39), and the C4-C24 fragment of macrolactin A (Scheme 40).…”

“…As in the case of organoboron reagents, organostannanes and organosilanes have mostly been used in asymmetric allylation reactions, and this topic is well covered by reviews. [117,119] However, the allylation of a,b-unsaturated carbonyl compounds has been elegantly employed in various total syntheses, including the synthesis of papulacandin D (Scheme 38), [120,121] topsentolide B 3 [122] (Scheme 39), and the C4-C24 fragment of macrolactin A (Scheme 40). [123] These illustrate once again the importance of chiral allylic alcohols as structural motifs in natural products and their utility as building blocks for further transformations.…”

Katalytische asymmetrische Synthese von Allylalkoholen und Allylalkohol‐Derivaten und deren Anwendung in der organischen Synthese

“…119 Allerdings wurde die Allylierung von α,β‐ungesättigten Carbonylverbindungen auf elegante Weise in verschiedenen Totalsynthesen eingesetzt, z. B. in der Synthese von Papulacandin D (Schema ),120, 121 von Topsentolid B 3 122 (Schema ) und des C4‐C24‐Fragments von Macrolactin A (Schema ) 123. Dies illustriert noch einmal die Bedeutung chiraler Allylalkohole als Strukturmotive in Naturstoffen und ihre Nützlichkeit als Bausteine für weitere Transformationen.…”