Concise Synthesis of Ansellone A

Concise Synthesis of Ansellone A

Author: ChemistryViews.org

Human immunodeficiency virus (HIV) infections can usually be managed well using antiretroviral drugs. However, this is no cure for HIV because the virus persists in the body and can re-emerge if the treatment is stopped. One strategy towards developing a cure for HIV uses so-called latency-reversing agents (LRAs). LRAs reactivate virus production in latently infected cells and trigger an immune response and/or cell death. Ansellone A (pictured) is a marine sesterterpenoid that shows LRA activity. It has been synthesized in 24 total steps [1], but there is a lack of biological studies of ansellone A and its analogues.

Kenichi Murai, Mitsuhiro Arisawa, Osaka University, Japan, and colleagues have developed a concise synthesis of Ansellone A with 17 total steps and conducted a biological screening of this compound, as well as analogues with other substituents in the place of its –OAc group. The team started from (+)-sclareolide, which was first converted to a diol, then to a triflate-stabilized tertiary allylic alcohol, and finally oxidized to introduce an aldehyde group. The resulting intermediate was subjected to a Prins cyclization reaction with cis-γ-hydroxycarvone to create the tetrahydropyran ring of the target compound. Finally, the triflate group was removed and the acetate substituent was introduced to give ansellone A.

The researchers obtained ansellone A in 17 total steps with a longest linear sequence (LLS) of 13 steps from (+)-sclareolide. They also synthesized analogues with –OH or –OMe groups in place of the acetate substituent for bioactivity studies. The team found that the free alcohol has a higher LRA activity than the parent compound.



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