Solid‐Supported Synthesis of Bicyclic Peptides Containing Three Parallel Peptide Chains

Abstract

Four homodetic bicyclic peptides 9a−d, containing three parallel peptide chains, were synthesized on a hydroxymethylfunctionalized polystyrene support. α,α-Bis(aminomethyl)-β-alanine, bearing orthogonal protections (Alloc, Boc, Fmoc) on the three amino groups (1), was attached to the support through an H 2 N-Leu-Leu-Gly-OH spacer, and the peptide chains were assembled on the amino groups of 1 by either a stepwise coupling or coupling of a segment, keeping the amino protection within each chain unchanged. N-(4-Allyloxy-4-oxobutanoyl)iminodiacetic acid (2) was then coupled to the

Synthesis of Biotinylated Multipodal Glycoclusters on a Solid Support

“…The final theoretical loading can be calculated by Equation (1): [45] L final = L initial /(ΔM ϫ L initial + 1) (1) where L final stands for the final theoretical loading [mol g -1 ], L initial for the initial measured loading [mol g -1 ], and ΔM for the change in the molecular mass of the product. The final theoretical loading can be calculated by Equation (1): [45] L final = L initial /(ΔM ϫ L initial + 1) (1) where L final stands for the final theoretical loading [mol g -1 ], L initial for the initial measured loading [mol g -1 ], and ΔM for the change in the molecular mass of the product.…”

“…Overall yields of the conjugates were calculated by taking the change in the molecular mass of the product into account. The final theoretical loading can be calculated by Equation (1): [45] L final = L initial /(ΔM ϫ L initial + 1) (1) where L final stands for the final theoretical loading [mol g -1 ], L initial for the initial measured loading [mol g -1 ], and ΔM for the change in the molecular mass of the product.…”

Solid-Supported Synthesis of Cryptand-like Macrobicyclic Peptides

“…Another approach exploits conjugate group mediated cyclization: a support-bound peptide bearing one 3,5-dihydroxybenzoyl and two 2-fluoro-5-nitrobenzoyl residues is subjected to a SnAr displacement of the fluoro substituents by the benzoyl hydroxy groups . We have recently reported on a solid-supported synthesis of spirobicyclic peptides and bicyclic peptides containing three parallel peptide chains . These syntheses have been based on bis(aminomethyl)malonic acid and bis(aminomethyl)-β-alanine as branching units.…”

Peptide Macrocycles Featuring a Backbone Secondary Amine: A Convenient Strategy for the Synthesis of Lipidated Cyclic and Bicyclic Peptides on Solid Support

“…A recent investigation of novel polymyxin analogs obtained with a combination of solid-phase synthesis and solution-phase cyclization resulted in similar or lower yields . Karskela et al reported ≤5% yields for their solid-supported synthesis of fused bicyclic peptides, whereas 12 (Figure ) was obtained in 19.6% yield.…”