Related Experiment Video
Updated: May 8, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Template-induced macrocycle diversity through large ring-forming alkylations of tryptophan
Kenneth V Lawson1, Tristan E Rose, Patrick G Harran
1Department of Chemistry and Biochemistry, University of California Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569 (USA).
Abstract:
Macrocyclic peptidomimetics are valuable in research and serve as lead compounds in drug discovery efforts. New methods to prepare such structures are of considerable interest. In this pilot study, we show that an organic template harboring a latent cinnamyl cation participates in novel Friedel-Crafts macrocyclization reactions with tryptophan. Upon joining the template to Trp-Trp-Tyr, a single operation efficiently generates eight unique macrocycles. Each has been isolated and thoroughly characterized. Product distribution as a function of Brønsted and/or Lewis acidic conditions was explored, and outcomes were compared to rearrangements induced within a corresponding tyrosine-linked cyclic ether. The solution structure of a new macrocyclic pyrroloindoline was solved using a combination of two-dimensional NMR methods and molecular mechanics simulations. Template-induced structural diversification of peptide sequences harboring aromatic residues has potential to create myriad macrocycles that target surfaces involved in protein-protein interactions.
Related Concept Videos
Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)
Cycloaddition Reactions: Overview
Amino Acid Biosynthetic Pathways
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Cycloaddition Reactions: MO Requirements for Photochemical Activation
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
