Total Synthesis of Waltherione F, a Nonrutaceous 3-Methoxy-4-quinolone, Isolated from Waltheria indica L. F.

Abstract

Waltherione F was totally synthesized in seven steps and 31% overall yield from 2-nitro-3-methylanisole without the use of protecting groups. Key steps in the sequence were a Suzuki-Miyaura coupling to attach the n-octyl chain and a microwave-promoted cyclization of an acetonyl anthranilate to give the heterocyclic core whose 3-OH was O-methylated.

The Synthesis of Waltherione F and Its Analogues with Modifications at the 2‐ and 3‐Positions as Potential Antitrypanosomal Agents

“…[12] The authors would like to note that after completion of this work, as ynthesis of waltherione F 3 using an alternative synthetic approach has appeared. [13] Conclusion Waltherione F 3 was synthesised in 5-step reactions equence. One of the key reactions was the formation of 8-methoxy-2methyl-5-octylquinolin-4(1H)-one 23 which was achieved within 6h ours which was an improvemento ft he two-week synthesis reported in the literature for similarc ompounds.…”

“…The authors would like to note that after completion of this work, a synthesis of waltherione F 3 using an alternative synthetic approach has appeared …”

Efficient Synthesis of 7H‐Chromeno[3,2‐c]quinolin‐5‐ium Salts and Quinolin‐4‐ones through Acid‐Promoted Cascade Reaction of 3‐Formylchromones and Anilines

“…Quinolones have received much attention in recent years. They are commonly found in natural products [27] and play a pivotal role in drug development [28,29] . Furthermore, quinolones may also act as versatile building blocks in organic synthesis [30] .…”

Access to 2-Alkyl/Aryl-4-(1H)-Quinolones via Orthogonal “NH3” Insertion into o-Haloaryl Ynones: Total Synthesis of Bioactive Pseudanes, Graveoline, Graveolinine, and Waltherione F

“…In addition, an -OMe group ortho to the carbonyl was introduced in two steps involving NBS-mediated bromination and CuI-catalyzed S N Ar type displacement with NaOMe to deliver waltherione F 17 (six steps, 33% overall yield) and the value was found to be spectroscopically identical with the values reported for the natural product (see the Supporting Information). ,, …”

“…3c Waltherione F is notable for exhibiting antitrypanosomal activity against Trypanosoma cruzi, a parasite that causes Chagas disease. To date, two total syntheses of natural product 17 have been reported by Larghi et al 18 utilizing Suzuki− Miyaura coupling and microwave-assisted cyclization as the key reactions (seven steps, 31% overall yield) and by Cox et al 19 employing Conrad−Limpach synthesis as a key step (five steps, 11% overall yield).…”