Asymmetric Total Synthesis of (-)-Arborisidine and (-)-19-epi -Arborisidine Enabled by a Catalytic Enantioselective Pictet-Spengler Reaction

Journal of the American Chemical Society
Rémi AndresJieping Zhu

Abstract

A five-step total synthesis of arborisidine, a caged pentacyclic monoterpene indole alkaloid, has been accomplished in both racemic and enantioselective manners. The synthesis features the following three key steps: (a) a regioselective Pictet-Spengler reaction of tryptamine with 2,3-pentanedione; (b) a chemo- and stereoselective intramolecular oxidative cyclization; and (c) a complexity-generating aza-Cope/Mannich cascade followed by in situ oxidation and epimerization. A chiral pyrenylpyrrolidino-squaramide catalyzed enantioselective Pictet-Spengler reaction between tryptamine and 2,3-pentanedione is subsequently uncovered, allowing us to develop a five-step asymmetric synthesis of (-)-arborisidine, an enantiomer of the natural substance. Both (±)-19-epi-arborisidine and (-)-19-epi-arborisidine are also synthesized, which undergo epimerization at room temperature in the presence of aqueous 2 N KOH to (±)-arborisidine and (-)-arborisidine, respectively. The 19-epi-isomer is also partially epimerized to arborisidine upon preparative TLC purification (eluent: MeOH/CHCl3 saturated with NH3) and equilibrium studies indicate that arborisidine is thermodynamically more stable than its 19-epimer. In line with Kam's biosynthesis propo...Continue Reading

References

Aug 26, 2004·Journal of the American Chemical Society·Mark S Taylor, Eric N Jacobsen
Jan 26, 2006·Journal of the American Chemical Society·Jayasree SeayadBenjamin List
Mar 23, 2007·Nature·Phil S BaranJeremy M Richter
Aug 19, 2007·Angewandte Chemie·Martin J WannerHenk Hiemstra
Oct 19, 2007·Journal of the American Chemical Society·Izzat T RaheemEric N Jacobsen
Jul 12, 2008·The Journal of Organic Chemistry·Nishant V SewgobindHenk Hiemstra
May 8, 2009·Chemical Society Reviews·Zhiguo Zhang, Peter R Schreiner
Jul 18, 2009·Journal of the American Chemical Society·Michael E MuratoreDarren J Dixon
Mar 12, 2010·Journal of the American Chemical Society·Connor L MartinJason M Rohde
Sep 4, 2010·Journal of the American Chemical Society·Zhiwei ZuoDawei Ma
May 11, 2011·Journal of the American Chemical Society·Liansuo ZuNeil K Garg
May 19, 2011·Chemistry : a European Journal·José AlemánKarl Anker Jørgensen
Oct 19, 2011·Angewandte Chemie·Zhiwei Zuo, Dawei Ma
Jan 28, 2012·Journal of the American Chemical Society·Gregory L AdamsAmos B Smith
Feb 23, 2012·Chemistry : a European Journal·Dan HuangYanguang Wang
Mar 24, 2012·Tetrahedron Letters·Joseph J BadilloAnnaliese K Franz
May 24, 2012·Journal of the American Chemical Society·Weiwei ZiDawei Ma
Nov 30, 2012·Angewandte Chemie·Katrien Brak, Eric N Jacobsen
Dec 28, 2012·Journal of the American Chemical Society·Gregory L AdamsAmos B Smith
Feb 13, 2013·Chemistry : a European Journal·Tsugunori WatanabeTsunehiko Higuchi
Feb 26, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mingxue SunKai Xiao
Mar 9, 2013·European Journal of Organic Chemistry·Fenghai GuoRegan J Thomson
Jun 13, 2013·Chemical Communications : Chem Comm·Hongzhi YangYefeng Tang
Aug 24, 2013·Journal of the American Chemical Society·Myles W Smith, Scott A Snyder
Sep 24, 2013·Organic & Biomolecular Chemistry·Olga V SerdyukSvetlana B Tsogoeva
Jan 24, 2014·Angewandte Chemie·Weiwu RenJieping Zhu
Feb 1, 2014·Angewandte Chemie·Mingxing TengDawei Ma
Jun 19, 2015·Tetrahedron Letters·Richard Y LiuEric N Jacobsen
Feb 5, 2016·Angewandte Chemie·Weiwu RenJieping Zhu
Mar 11, 2016·Journal of the American Chemical Society·Yong LiAng Li
Aug 26, 2016·Journal of the American Chemical Society·Cyril PiemontesiJieping Zhu
Jan 11, 2017·Chemistry : a European Journal·Ruben EckermannTanja Gaich

❮ Previous
Next ❯

Citations

Mar 6, 2021·Natural Product Reports·Audrey MaugerGuillaume Vincent
Mar 30, 2021·Angewandte Chemie·Feng-Yuan Wang, Lei Jiao
May 18, 2021·Chemical Science·Tessa Lynch-ColametaScott A Snyder
Jun 16, 2021·The Journal of Organic Chemistry·Hussein Abou-HamdanGuillaume Vincent
Nov 9, 2021·Journal of the American Chemical Society·Chunngai HuiAndrey P Antonchick
Oct 20, 2021·Angewandte Chemie·Cheng WangZhiqiang Ma

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.