Solid Phase Synthesis of Vancomycin Mimics

Abstract

A solid phase synthesis of a model system of the DE ring system of vancomycin is described. The synthesis involved biocatalytic resolutions of unnatural amino acids, is compatible with conventional solid phase peptide synthesis and contains as the key step: an on-bead S N Ar cyclization. Binding

Microwave-Assisted Solid-Phase Synthesis of a 1,2-Disubstituted Benzimidazole Library by Using a Phosphonium Linker

“…The synthesis of the benzimidazole derivatives started with the preparation of the 4‐fluoro‐3‐nitrobenzyl iodide 3 from 4‐fluorobenzaldehyde 1 (Scheme ) . After nitration reaction and subsequent NaBH 4 reduction of aldehyde group, the resulting benzylic alcohol 2 was converted into iodide 3 using PS‐TPP‐iodine complex in dry dichloromethane with 45% yield after 48 h at room temperature .…”

Bioactive Macrocyclic Peptides and Peptide Mimics

“…With respect to this, Ellman and coworkers [16], Zhu and coworkers [17], Arnusch and Pieters [18], and Liskamp and coworkers [19] have prepared (monocyclic) mimics of the D-E part of the cavity of these antibiotics via an intramolecular nucleophilic aromatic substitution [16][17][18] or a Sonogashira-based macrocyclization [19] (Figure 1.4). Recently, a bicyclic mimic of the C-D-E cavity, which was prepared by a Stille reaction followed by tandem ring-closing metathesis (9, Figure 1.4), was described by Liskamp and coworkers [20].…”

Estratégias utilizadas no combate a resistência bacteriana

“…Simplificações na estrutura da vancomicina, mantendo apenas o núcleo constituído pelos anéis aromáticos D e E, foram efetuadas a partir da química de peptídeos, em trabalhos independentes 45,48,49 . Desproteção e ciclização do tetrapeptídeo 5, obtido a partir de reações consecutivas de acoplamento dos respectivos aminoácidos em fase sólida, seguido de clivagem do suporte sólido forneceu o peptídeo cíclico 6, pertencente a uma classe de compostos com atividade biológica diversificada 49 (Esquema 5).…”

“…Desproteção e ciclização do tetrapeptídeo 5, obtido a partir de reações consecutivas de acoplamento dos respectivos aminoácidos em fase sólida, seguido de clivagem do suporte sólido forneceu o peptídeo cíclico 6, pertencente a uma classe de compostos com atividade biológica diversificada 49 (Esquema 5).…”