Installing amino acids and peptides on N-heterocycles under visible-light assistance

Abstract

Readily available natural α-amino acids are one of nature’s most attractive and versatile building blocks in synthesis of natural products and biomolecules. Peptides and N-heterocycles exhibit various biological and pharmaceutical functions. Conjugation of amino acids or peptides with N-heterocycles provides boundless potentiality for screening and discovery of diverse biologically active molecules. However, it is a great challenge to install amino acids or peptides on N-heterocycles through formation of carbon-carbon bonds under mild conditions. In this article, eighteen N-protected α-amino acids and three peptides were well assembled on phenanthridine derivatives via couplings of N-protected α-amino acid and peptide active esters with substituted 2-isocyanobiphenyls at room temperature under visible-light assistance. Furthermore, N-Boc-proline residue was successfully conjugated with oxindole derivatives using similar procedures. The simple protocol, mild reaction conditions, fast reaction, and high efficiency of this method make it an important strategy for synthesis of diverse molecules containing amino acid and peptide fragments.

Visible‐Light Photoredox Decarboxylative Couplings

“…Recently, our group developed the visible‐light photoredox coupling reaction of N ‐protected amino acids 112 with substituted 2‐isocyanobiphenyls 113 at room temperature with the assistance of the [Ru(bpy) 3 ]Cl 2 photocatalyst (Scheme ) . The method provided the biologically and pharmaceutically active phenanthridine derivatives 114 in good yields and was successfully applied to the conjugation of phenanthridines with peptides (such as 115 and 116 ).…”

Decarboxylative couplings as versatile tools for late‐stage peptide modifications

“…Decades after the initial disclosure of decarboxylative transformations using the versatile activated esters outlined in Schemes and , the synthetic utility of these venerable intermediates became a source of renewed excitement, owing to the seminal work of several research groups . The pivotal realization—that carbon‐centered radicals (e.g., 18 ) formed through decarboxylation of activated alkyl esters can engage in conventional cross‐coupling pathways—markedly expanded the retrosynthetic utility of carboxylic acid derivatives.…”

“…Given the overlap between redox‐active esters (RAEs) and the intermediates formed using standard peptide coupling reagents, it is perhaps unsurprising that RAEs have gradually emerged as powerful tools for the coupling of peptide‐based alkyl carboxylic acids. In addition to a variety of nickel‐catalyzed transformations, concurrent work has exploited Okada's photoinduced fragmentation of phthalimide esters for the decarboxylative arylation, thiolation, and selenation of peptide substrates ( vide infra ). Despite a conceptual similarity to prior work on decarboxylative functionalizations, the renewed impetus for the contemporary advancement of RAE‐mediated decarboxylative couplings stems largely from a growing demand for modified peptides from both academia and industry.…”

“…In 2016, H. Fu and coworkers reported a collection of high‐yielding, photochemical decarboxylative peptide α‐arylations employing NHPI esters (Scheme ) . The authors first disclosed the visible‐light assisted, ruthenium‐catalyzed coupling of peptide RAEs such as 48 with 2‐isocyanobiphenyl 49 to afford the 8‐methylphenanthridine derivatives 50 ‐ 52 in excellent yields (Scheme ) . An intriguing modification of the protocol allowed formation of pentapeptide 52 in the absence of a conventional photocatalyst .…”

Olefination of Alkyl Halides with Aldehydes by Merging Visible-Light Photoredox Catalysis and Organophosphorus Chemistry

“…Recently, photoredox catalysis has become a powerful strategy for the activation of molecules, and some unprecedented reactions have been developed, thanks to the ability of photoredox catalysts to cleanly transform visible light into prominent levels of chemical energy ( Hari and König, 2013 , Ravelli et al., 2009 , Jin and Fu, 2017 , König, 2013 , Narayanam and Stephenson, 2011 , Shaw et al., 2016 , Shi and Xia, 2012 , Xuan and Xiao, 2012 , Yoon et al., 2010 , Zeitler, 2009 ). For the past year, we have indeed developed some valuable visible-light photoredox organic reactions ( Gao et al., 2016 , Jiang et al., 2016a , Jiang et al., 2016b , Jiang et al., 2016c , Jiang et al., 2017 , Jin et al., 2016a , Jin et al., 2016b , Jin et al., 2016c , Jin et al., 2017 , Li et al., 2016 ). Inspired by the robustness and excellent achievements of photoredox catalysis, we hypothesized that a straightforward procedure might be developed to enable C=C bond formation via coupling of alkyl halides with aldehydes and their derivatives using triphenylphosphine as a reductive quencher.…”