Divergent Total Syntheses of ITHQ-type Bis-β-carboline Alkaloids by Regio-selective Formal Aza-[4 + 2] Cycloaddition and Late-stage C-H Functionalization

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Sep 29

PMID 37772099

Authors

Qixuan Wang

Fusheng Guo

Jin Wang

Xiaoguang Lei

Affiliations

Soon will be listed here.

Abstract

We herein report the first total syntheses of several bis-β-carboline alkaloids, picrasidines G, S, R, and T, and natural product-like derivatives in a divergent manner. Picrasidines G, S, and T feature an indolotetrahydroquinolizinium (ITHQ) skeleton, while picrasidine R possesses a 1,4-diketone linker between two β-carboline fragments. The synthesis of ITHQ-type bis-β-carboline alkaloids could be directly achieved by a late-stage regio-selective aza-[4 + 2] cycloaddition of vinyl β-carboline alkaloids, suggesting that this remarkable aza-[4 + 2] cycloaddition might be involved in the biosynthetic pathway. Computational studies revealed that such aza-[4 + 2] cycloaddition is a stepwise process and explained the unique regioselectivity (ΔΔ = 3.77 kcal mol). Moreover, the successful application of iridium-catalyzed C-H borylation on β-carboline substrates enabled the site-selective C-8 functionalization for efficient synthesis and structural diversification of this family of natural products. Finally, concise synthesis of picrasidine R by the thiazolium-catalyzed Stetter reaction was also accomplished.

Citing Articles

Picrasidine S Induces cGAS-Mediated Cellular Immune Response as a Novel Vaccine Adjuvant.

Ding X, Sun M, Guo F, Qian X, Yuan H, Lou W Adv Sci (Weinh). 2024; 11(32):e2310108.

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