Exceedingly Concise and Elegant Synthesis of (+)-Paniculatine, (−)-Magellanine, and (+)-Magellaninone

Abstract

Starting from inexpensive (+)-pulegone as the chiral building block, a highly convergent synthesis of the unusual diquinane-based structures of (+)-paniculatine (1), (-)-magellanine (2), and (+)-magellaninone (3), has been achieved. This approach is based upon a tandem acylation-alkylation of ketoester 8 and palladium-catalyzed olefin insertion, oxidation, and hydrogenation for construction of the tetracyclic framework. This exceedingly concise strategy, requiring only 12-14 steps, is the shortest to date.

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…Construction of the tetracyclic scaffolds of these alkaloids and also controlling the stereochemistry at a multitude of the carbon centers of the bicyclo[3.3.0]octane core certainly represent daunting synthetic challenges. 405 − 409 …”

Enantioselective Synthesis of cis‐Decalin Derivatives by the Inverse‐Electron‐Demand Diels–Alder Reaction of 2‐Pyrones

“…[10] Retrosynthetically, this motif could be obtained from 2-pyrone 1 and 5-methyl-substituted silyl cyclohexadienol ether 2 k via the current reaction. Compound 2 k would be obtained in one step from 5methylcyclohex-2-en-1-one 5 k, whose two enantiomers could be readily prepared from chiral isopulegol [11] or from easily available starting materials by asymmetric catalysis. [12] We supposed if the current ytterbium catalysis exerted good stereocontrol on this reaction, then the stereodivergent synthesis [13] of methyl-substituted cis-decalin scaffolds could be achieved.…”

A Concise Total Synthesis of (+)‐Paniculatine

“…By using an intramolecular aldol reaction, Yang accomplished a collective total synthesis of the tetracyclic diquinane Lycopodium alkaloids and analogues thereof in 25–28 steps in 2014 . Soon after Yang's report, Yan described an elegant palladium‐catalyzed olefin insertion to access (+)‐paniculatine, (−)‐magellanine, and (+)‐magellaninone in 12 steps . In addition to these total syntheses, several synthetic studies on the formation of the tetracyclic framework of (+)‐paniculatine have also been published in the literature .…”

“…[5] Soon after Yang's report, Yan described an elegant palladium-catalyzed olefin insertion to access (+)-paniculatine, (À )-magellanine, and (+)-magellaninone in 12 steps. [6] In addition to these total syntheses, several synthetic studies on the formation of the tetracyclic framework of (+)-paniculatine have also been published in the literature. [7] Herein, we wish to report a concise total synthesis of (+)-paniculatine from simple starting materials.…”

“…As shown in Scheme 3, chemoselective silylation of diketone 5 with TBSCl/NaH in THF at 0°C proceeded smoothly to give the corresponding TBS ether 12 in 86% yield. [6] After diastereoselective reduction of the remaining carbonyl group with Lselectride, LiAlH 4 was added to reduce the amide at 75°C. After addition of HCl and stirring for 2 h, the final product (+)-paniculatine (1) was obtained in 82% yield.…”