A General Approach to Cyathin Diterpenes. Total Synthesis of Allocyathin B₃

Abstract

[reaction: see text] The synthesis of allocyathin B(3) from an advanced intermediate possessing the ring system and relative stereochemistry but lacking the isopropyl and hydroxymethyl groups is reported. The isopropyl group was introduced by radical cyclization of a methyl propargyl acetal of an alpha-bromo ketone, and the hydroxymethyl group was generated by Pd-catalyzed carbonylation of a vinyl triflate. The route provides functionalized intermediates that could allow access to more complex members of the cyathin family of diterpenes.

Photochemische Reaktionen als Schlüsselschritte in der Naturstoffsynthese

“…Als synthetisches ¾quivalent für Propylen oder Keten dient in der [2+2]-Photocycloaddition mitunter Allen. Anwendungen finden sich in den Synthesen von (AE )-Atisin, [293] (À)-Annotinin, [294] (AE )-Allocyathin B 3 , [295] (À)-Cyathin A 3 , [296] (AE )-Heliannuol D [297] und (AE )-Pentalenen. [298] Weitere intermolekulare Zugangswege zum racemischen und zum enantiomerenreinen Kelsoen (216) [299] wurden ebenso beschrieben wie eine der oben gezeigten Strategie folgende Synthese des strukturell verwandten (À)-Sulcatin G. [300] Ein alternativer Zugang zu (AE )-Kelsoen (216) bediente sich der intramolekularen Cu-katalysierten [2+2]-Photocycloaddition (Schema 57).…”

Enantioselective Total Synthesis of Cyathin A3

“…149 In principle, a 1-methyl-2-propenyl substituent could be transformed into an isopropyl group by oxidative cleavage of the olefin followed by reduction. In previous work, 47 …”

“…46 Ward extended this work and was able to accomplish the total synthesis of racemic allocyathin B 3 . 47 Ward's synthesis was the first general route providing both the trans 6-7 ring fusion and the fully functionalized seven-membered ring, that with simple modifications might be applied to the synthesis of any of the known cyathin diterpenes, as well as several related natural products. …”

7-6-5 Tricarbocyclic Diterpenes

“…5.18 appears the tricyclic diterpenes with a 7-6-5 system not synthesized until now. Synthesized cyathanes are (AE)-allocyathin B 2 and (+)-erinacine A [160,161], (AE)-allocyathin B 2 [162,163], (+)-allocyathin B 2 [164,165], (AE)-sarcodonin G [68], (AE)-allocyathin B 3 [166][167][168], (À)-cyathin A 3 [168,169], (À)-erinacine B [170], (À)-erinacine E [171], (À)-scabronine G [172], (+)-cyanthiwigin U [173], (+)-cyanthiwigin W [173], (À)-cyanthiwigin Z [173], (+)-cyanthiwigin AC [174], and (À)cyanthiwigin F [175]. Until 2009, cyathane syntheses have been collected in the excellent reviews of Wright and Whitehead [3] and Enquist and Stoltz [4].…”