Asymmetric Total Synthesis of (−)-Scabronine G via Intramolecular Double Michael Reaction and Prins Cyclization

Abstract

The enantioselective total synthesis of (-)-scabronine G is described. The key features of the present synthesis include the construction of a 5-6 ring system containing two quaternary carbon centers via a diastereoselective intramolecular double Michael reaction and the formation of a seven-membered ring using a Prins cyclization.

7-6-5 Tricarbocyclic Diterpenes

“…Among them can be seen a valparane derivative, a considerable number of cyathane derivatives, and three verrucosane derivatives. The synthesis of cyanthiwigin B, F, and G [176], cyathin A 3 and cyathin B 2 [177], cyrneine A [178], scabronines G [179,180], and A [180], episcabronine A [180], cyanthiwigin A, C, G, and H [181] and scabronine D [182], cyathin B 2 [183], and the synthesis of a valparane derivative [184] and verrucosane derivatives [185] such as (AE)-verrucosan-2S-ol, (AE)-neoverrucosan-5R-ol, and (AE)-homoverrucosa-2-en-5S-ol, will be shown. 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].…”

“…Kanoh Synthesis of (2)-Scabronine G In 2011, Kanoh and coworkers described the synthesis of (À)-scabronine G 130 [179]. The scabronine G 130 tricyclic system with two quaternary carbon centers was carried out via diastereoselective intramolecular double Michael (IDM) reaction and Prins cyclization (Scheme 5.10).…”

Neurotrophic Natural Products: Chemistry and Biology

“…[168] Key to this synthesis was an intramolecular double 1,4-addition of 170 under TMSI/HMDS conditions, which afforded the bridged tricyclic scaffold of 171 . Another critical step was a Lewis acid induced Prins cyclization of 172 to construct the seven-membered ring of 173 .…”

“…Part of the total synthesis of (−)-scabronine G ( 152 ) by Kanoh, Iwabuchi et al [168] HMDS =hexamethyldisilazane.…”

2.03 Prins Reactions and Carbonyl, Imine, and Thiocarbonyl Ene Reactions

“…175 Under the acidic reaction conditions the allylic methyl ether undergoes partial solvolysis to give the alcohol. Me 2 AlCl-induced ene reaction of 318 affords enol ether alcohol 319 in 87% yield, which was elaborated to (-)-scarbonine G. 176 Marshall has shown that type II ene reactions of alkynals can be used to form 12-, 14-, and 16-membered rings. 147 For instance, treatment of 320 with EtAlCl 2 affords 321 with a 16-membered ring in 84% yield.…”