Tandem Deprotection–Dimerization–Macrocyclization Route to C2 Symmetric cyclo‐Tetrapeptides

Ha, Khanh; Lebedyeva, Iryna; Hamedzadeh, Sadra; Li, Zhiliang; Quiñones, Ryan; Pillai, Girinath G.; Williams, Byron; Nasajpour, Amir; Martin, Kristin; Asiri, Abdullah M.; Katritzky, Alan R.

doi:10.1002/chem.201304262

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…275 11. TANDEM DEPROTECTION−DIMERIZATION−MACROCYCLI-ZATION Ha et al 277 designed a procedure they refer to as "tandem deprotection−dimerization−macrocyclization" in which the Nterminally Cbz protected dipeptides were preactivated as the respective benzotriazolides (Scheme 17). The activated precursor was then deprotected and cyclized in a single step, resulting in dimerization and subsequent cyclization to yield a variety of C 2 symmetric CTPs in yields ranging 22−86%.…”

Section: -Membered Ctpsmentioning

confidence: 99%

Cyclic Tetrapeptides from Nature and Design: A Review of Synthetic Methodologies, Structure, and Function

et al. 2019

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Small cyclic peptides possess a wide range of biological properties and unique structures that make them attractive to scientists working in a range of areas from medicinal to materials chemistry. However, cyclic tetrapeptides (CTPs), which are important members of this family, are notoriously difficult to synthesize. Various synthetic methodologies have been developed that enable access to natural product CTPs and their rationally designed synthetic analogues having novel molecular structures. These methodologies include the use of reversible protecting groups such as pseudoprolines that restrict conformational freedom, ring contraction strategies, onresin cyclization approaches, and optimization of coupling reagents and reaction conditions such as temperature and dilution factors. Several fundamental studies have documented the impacts of amino acid configurations, N-alkylation, and steric bulk on both synthetic success and ensuing conformations. Carefully executed retrosynthetic ring dissection and the unique structural features of the linear precursor sequences that result from the ring dissection are crucial for the success of the cyclization step. Other factors that influence the outcome of the cyclization step include reaction temperature, solvent, reagents used as well as dilution levels. The purpose of this review is to highlight the current state of affairs on naturally occurring and rationally designed cyclic tetrapeptides, including strategies investigated for their syntheses in the literature, the conformations adopted by these molecules, and specific examples of their function. Using selected examples from the literature, an in-depth discussion of the synthetic techniques and reaction parameters applied for the successful syntheses of 12-, 13-, and 14-membered natural product CTPs and their novel analogues are presented, with particular focus on the cyclization step. Selected examples of the three-dimensional structures of cyclic tetrapeptides studied by NMR, and X-ray crystallography are also included. CONTENTSSpecial Issue: Macrocycles

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Section: -Membered Ctpsmentioning

confidence: 99%

Cyclic Tetrapeptides from Nature and Design: A Review of Synthetic Methodologies, Structure, and Function

et al. 2019

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“…The synthesis of cyclic peptides is often challenging. Benzotriazole methodology was extended to use in the synthesis of various cyclic peptides via dimerization macrocyclization approach [19] Figure [4][5][6].…”

Section: Benzotriazole In Cyclic Peptide Synthesismentioning

confidence: 99%

Benzotriazole: A Versatile Synthetic Auxiliary

Panda¹

2018

AOICS

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“…Reports on the successful preparation of cyclotetrapeptides containing a combination of αand β-amino acids using the metal template strategy can be found in the literature, which further substantiates the difficulty experienced when synthesising 12-membered cycles compared to 13-or 14-membered ring analogues. 63,64 For example, a Pd-promoted tandem deprotection/cyclisation dimerization method was used to prepare C 2 symmetrical cyclotetrapeptides from N-Cbz-dipeptidoyl benzotriazole (Bt) sequences (Cbz = carboxybenzyloxy) containing either βor αand β-amino acids (Scheme 8). 50 Tetrapeptides, linear or cyclic, were used to create molecularly imprinted cavities in polymer-cellulose composites.…”

Section: Organic and Biomolecular Chemistry Reviewmentioning

confidence: 99%

An update on new methods to synthesize cyclotetrapeptides

2015

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Cyclotetrapeptides are important bioactive lead drug molecules that display a wide spectrum of pharmacological activities. However, the synthesis of cyclotetrapeptides from their linear precursors is challenging due to the highly constrained conformation required for cyclisation, thus hampering their progress to a clinical setting. This review provides an account of the reported methods used for the synthesis of cyclotetrapeptides.

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Tandem Deprotection–Dimerization–Macrocyclization Route to C₂ Symmetric cyclo‐Tetrapeptides

Cited by 13 publications

References 39 publications

Cyclic Tetrapeptides from Nature and Design: A Review of Synthetic Methodologies, Structure, and Function

Cyclic Tetrapeptides from Nature and Design: A Review of Synthetic Methodologies, Structure, and Function

Benzotriazole: A Versatile Synthetic Auxiliary

An update on new methods to synthesize cyclotetrapeptides

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