On the prevalence of bridged macrocyclic pyrroloindolines formed in regiodivergent alkylations of tryptophan. Issue 7 (16th March 2016)

• Record Type: Journal Article
• Authors: Rose, Tristin E.; Curtin, Brice H.; Lawson, Kenneth V.; Simon, Adam; Houk, K. N.; Harran, Patrick G.
• Is Part Of: Chemical science. Volume 7:Issue 7(2016:Jul.)
• Page Start: 4158
• Page End: 4166
• Publication Date: 2016-03-16
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5sc04612b
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Brønsted acid promotes internal cinnamylations of tryptophan to form structurally complex pyrroloindolines within unique collections of ansa-bridged composite macrocycles. Abstract : A Friedel–Crafts alkylation is described that efficiently transforms tryptophan-containing peptides into macrocycles of varying ring connectivity. Factors are surveyed that influence the distribution of regioisomers, with a focus on indole C3-alkylations leading to bridged endo -pyrroloindolines. We probe the stability and stereochemistry of these pyrroloindolines, study their rearrangement to C2-linked indolic macrocycles, and demonstrate a scalable, stereoselective synthesis of this compound class. Placing the macrocyclization in sequence with further template-initiated annulation leads to extraordinary polycyclic products and further demonstrates the potential for this chemistry to drive novel peptidomimetic lead discovery programs.