Total Synthesis of Ansellone G and Phorbadione

Abstract

The first total synthesis of marine sesterterpenoid ansellone G (2) was accomplished. This strategy utilizes the Prins cyclization reaction of a chloro-substituted homoallyl alcohol to synthesize the hydrobenzopyran skeleton. The preintroduction of the chloro groups facilitated the functional group transformation for 2 after constructing the carbon framework. Furthermore, we also successfully synthesized phorbadione (3) by dehydrating the tertiary alcohol. The HIV latency-reversing activity of the synthesized 2, 3, and deacetylated 2 was also evaluated.

Synthesis and Biological Evaluation of Simplified Ansellone Analogues with Lipophilic Side Chains as HIV Latency‐Reversing Agents

“…General procedure for the synthesis of compounds 4 a–4 g, 4 i–4 k : TMSOTf (0.250 mL, 0.250 mmol, 1 M in toluene) was added dropwise to a mixture of alcohol 6 [23] (50.0 mg, 0.249 mmol), corresponding aldehyde (0.750 mmol) in toluene (2.6 mL) at −78 °C under N 2 atmosphere. After stirring at 0 °C for 1 h, saturated NaHCO 3 aq.…”

“…The hydrobenzopyrans examined in this study were synthesised according to Scheme 1, which uses a Prins cyclisation reaction to provide facile access to the hydrobenzopyran skeleton, a strategy that was recently developed during the development of our total syntheses of ansellane-type natural products, such as ansellone A, ansellone G, and phorbadione. [12,23] In particular, the Prins cyclizations of homoallylic alcohol 6 (which was prepared from (R)-carvone) with various readily available aldehydes, gave the corresponding hydrobenzopyrans 7. Subsequent nucleophilic substitution of the allylic chloride with NaOAc afforded compounds 8 in moderate yields over two steps from 6.…”

Marine natural products

“…449 Use of computer-assisted retro-synthetic analysis of the pupukeanane class of sesquiterpenoid MNPs identied several routes with unusual disconnections beyond those already precedented for manufacture of the compounds. 450 Diterpenoids ansellone G and hamigeran F, 451,452 eight phorbaketal congeners, 453 aromatic sterol myrmenaphthol A, and seco-sterols glaciasterol B and 6ketoaplidiasterol B have been synthesised for the rst time. 454,455 Complex tropolone-containing triterpenoid gukulenin B has also been prepared.…”