Bulky α,β-dehydroamino acids: their occurrence in nature, synthesis, and applications

Jiang, Jintao; Ma, Zhiwei; Castle, Steven L.

doi:10.1016/j.tet.2015.06.001

Cited by 46 publications

(31 citation statements)

References 221 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,2 The DKP and dehydroamino acid structural elements can reside in the same molecule. Often termed alkylidene diketopiperazines, these molecules are a medicinally privileged scaffold found in several natural products.…”

Section: Introductionmentioning

confidence: 99%

“…Construction of alkylidene diketopiperazines has often been established by combining traditional peptide coupling methods and classic strategies for dehydroamino acid synthesis. 2,3 The synthesis of alkylidene DKPs derived from unnatural amino acid precursors can be somewhat more arduous due to construction of the requisite precursors. A selection of monoalkylidene natural products (1–3) are illustrated that have been the focus of major synthetic efforts.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin

2017

View full text Add to dashboard Cite

The synthesis of barettin, a selective serotonin receptor inhibitor and potent antibiofouling natural product, is described. The synthesis starts with the diketopiperazine nucleus intact and the side chains are installed using iterative aldol condensations. The route represents a general strategy for synthesis of a wide array of mono-alkylidene diketopiperazine structures, including those derived from non-canonical amino acid residues.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin

2017

View full text Add to dashboard Cite

show abstract

“…37 Amino acid variants with unsaturated side chains have also been described. 38 Further development of such noncanonical amino acids offers a potentially fruitful route for the design of specific PPI inhibitors.…”

mentioning

confidence: 99%

Side-Chain Conformational Preferences Govern Protein–Protein Interactions

Watkins¹,

Bonneau

Arora³

2016

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Protein secondary structures serve as geometrically constrained scaffolds for the display of key interacting residues at protein interfaces. Given the critical role of secondary structures in protein folding and the dependence of folding propensities on backbone dihedrals, secondary structure is expected to influence the identity of residues that are important for complex formation. Counter to this expectation, we find that a narrow set of residues dominates the binding energy in protein–protein complexes independent of backbone conformation. This finding suggests that the binding epitope may instead be substantially influenced by the side-chain conformations adopted. We analyzed side-chain conformational preferences in residues that contribute significantly to binding. This analysis suggests that preferred rotamers contribute directly to specificity in protein complex formation and provides guidelines for peptidomimetic inhibitor design.

show abstract

“…α,β-Didehydro-α-amino acids belong to nonproteinogenic amino acids widespread in nature. 1,2 They contain a double bond between the C α and C β carbon atoms which results in their planar conformation and fixed values of the φ and ψ torsion angles. These features endow them with particular conformational properties.…”

Section: Introductionmentioning

confidence: 99%

A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis

Wołczański

Lisowski

2018

Journal of Peptide Science

View full text Add to dashboard Cite

N-(tert-butyloxycarbonyl) or N-(9-fluorenylmethoxycarbonyl) dipeptides with C-terminal (Z)-α,β-didehydrophenylalanine (∆ Phe), (Z)-α,β-didehydrotyrosine (∆ Tyr), (Z)-α,β-didehydrotryptophan (∆ Trp), (Z)-α,β-didehydromethionine (∆ Met), (Z)-α,β-didehydroleucine (∆ Leu), and (Z/E)-α,β-didehydroisoleucine (∆ Ile) were synthesised from their saturated analogues via oxidation of intermediate 2,5-disubstituted-oxazol-5-(4H)-ones (also known as azlactones) with pyridinium tribromide followed by opening of the produced unsaturated oxazol-5-(4H)-one derivatives in organic-aqueous solution with a catalytic amount of trifluoroacetic acid or by a basic hydrolysis. In all cases, a very strong preference for Z isomers of α,β-didehydro-α-amino acid residues was observed except of the ΔIle, which was obtained as the equimolar mixture of Z and E isomers. Reasons for the (Z)-stereoselectivity and the increased stability of the aromatic α,β-didehydro-α-amino acid residue oxazol-5-(4H)-ones over the corresponding aliphatic ones are also discussed. It is the first use of such a procedure to synthesise peptides with the C-terminal unsaturated residues and a peptide with 2 consecutive ΔPhe residues. This approach is very effective especially in the synthesis of peptides with aliphatic α,β-didehydro-α-amino acid residues that are difficult to obtain by other methods. It allowed the first synthesis of the ∆Met residue. It is also more cost-effective and less laborious than other synthesis protocols. The dipeptide building blocks obtained were used in the solid-phase synthesis of model peptides on a polystyrene-based solid support. Peptides containing aromatic α,β-didehydro-α-amino acid residues were obtained with PyBOP or TBTU as a coupling agent with good yields and purities. In the case of aliphatic α,β-didehydro-α-amino acid residues, a good efficiency was achieved only with DPPA as a coupling agent.

show abstract

Bulky α,β-dehydroamino acids: their occurrence in nature, synthesis, and applications

Cited by 46 publications

References 221 publications

Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin

Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin

Side-Chain Conformational Preferences Govern Protein–Protein Interactions

A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis

Contact Info

Product

Resources

About