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

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 proposal and their purification protocol, we suspect that 19-epi-arborisidine could also be a natural product.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:142

Enthalten in:

Journal of the American Chemical Society - 142(2020), 33 vom: 19. Aug., Seite 14276-14285

Sprache:

Englisch

Beteiligte Personen:

Andres, Rémi [VerfasserIn]
Wang, Qian [VerfasserIn]
Zhu, Jieping [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 13.01.2021

Date Revised 13.01.2021

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1021/jacs.0c05804

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312684258