Peptide Modifications: Versatile Tools in Peptide and Natural Product Syntheses

Synlett ◽  
2019 ◽  
Vol 30 (11) ◽  
pp. 1289-1302 ◽  
Author(s):  
Phil Servatius ◽  
Lukas Junk ◽  
Uli Kazmaier
Keyword(s):  
Amino Acids ◽  
Natural Product ◽  
Bond Activation ◽  
Bond Formation ◽  
Side Chain ◽  
Peptide Backbone ◽  
Claisen Rearrangements ◽  
The Past ◽  
Allylic Alkylations ◽  
Peptide Modifications

Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses.1 Introduction2 Peptide Backbone Modifications via Peptide Enolates2.1 Chelate Enolate Claisen Rearrangements2.2 Allylic Alkylations2.3 Miscellaneous Modifications3 Side-Chain Modifications3.1 C–H Activation3.1.1 Functionalization via Csp3–H Bond Activation3.2.2 Functionalization via Csp2–H Bond Activation3.2 On Peptide Tryptophan Syntheses4 Conclusion

Gram-Scale Solution-Phase Synthesis of Heptapeptide Side Chain of Teixobactin

Synlett ◽  
2019 ◽  
Vol 30 (20) ◽  
pp. 2268-2272 ◽  
Author(s):  
Sangeetha Donikela ◽  
Kiranmai Nayani ◽  
Vishnuvardhan Nomula ◽  
Prathama S. Mainkar ◽  
Srivari Chandrasekhar
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Natural Product ◽  
Solution Phase ◽  
Side Chain ◽  
Phase Synthesis ◽  
Solution Phase Synthesis ◽  
Efficient Coupling ◽  
Scalable Synthesis

We report herein a scalable synthesis of linear heptapeptide side chain of the depsipeptide natural product teixobactin through solution phase. The synthesis of heptapeptide was achieved through an efficient coupling of suitably protected tripeptide and tetrapeptide comprising of three d-amino acids and four usual l-amino acid subunits.

Organoboron Reagents in the Preparation of Functionalized ?-Amino Acids

2007 ◽  
Vol 60 (11) ◽  
pp. 799 ◽  
Author(s):  
Peter F. Kaiser ◽  
Quentin I. Churches ◽  
Craig A. Hutton
Keyword(s):  
Amino Acids ◽  
Cyclic Peptide ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Side Chain ◽  
Coupling Reactions ◽  
The Past ◽  
Cross Coupling Reactions ◽  
Metal Catalyzed ◽  
Unsaturated Amino Acids

Over the past decade, major advances in the preparation and utilization of organoboron reagents have been applied to virtually all areas of organic synthesis. The present review collates recent examples of the use of organoboron reagents in the synthesis of α-amino acids and their derivatives. Aryl- and alkenylboronic acids have been used in the asymmetric synthesis of α-amino acids through conjugate addition to unsaturated amino acids and the Petasis three-component coupling reaction. Additionally, α-amino acid derivatives with organoboron functionality on the side-chain have been prepared and used in metal-catalyzed cross-coupling reactions to prepare cross-linked amino acids and complex cyclic peptide natural products.

scholarly journals Recent Developments in Palladium-Catalysed Non-Directed C–H Bond Activation in Arenes

Synthesis ◽  
2019 ◽  
Vol 51 (03) ◽  
pp. 643-663 ◽  
Author(s):  
Kåre Jørgensen ◽  
M. Fernández-Ibáñez ◽  
Sindhu Kancherla
Keyword(s):  
Aromatic Compounds ◽  
Bond Activation ◽  
Bond Formation ◽  
Short Review ◽  
The Past ◽  
New Approaches ◽  
Site Selectivity ◽  
Recent Developments ◽  
Directing Group

Over the past decades, organic chemists have focussed on developing new approaches to directed C–H functionalisations, where the site selectivity is steered by the presence of a directing group (DG). Nonetheless, in recent years, more and more non-directed strategies are being developed to circumvent the requisite directing group, making C–H functionalisations more generic. This short review focuses on the latest developments in palladium-catalysed non-directed C–H functionalisations of aromatic compounds.1 Introduction2 C–C Bond Formation2.1 C–H Arylation2.2 C–H Alkylation2.3 C–H Alkenylation2.4 C–H Carbonylation3 C–Heteroatom Bond Formation3.1 C–O Bond Formation3.2 C–N Bond Formation3.3 C–S Bond Formation4 Conclusion

scholarly journals Visible-light-mediated catalyst-free synthesis of unnatural α-amino acids and peptide macrocycles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mengran Wang ◽  
Chao Wang ◽  
Yumei Huo ◽  
Xiaobo Dang ◽  
Hongxiang Xue ◽  
...  
Keyword(s):  
Amino Acids ◽  
Visible Light ◽  
Unnatural Amino Acids ◽  
Homolytic Cleavage ◽  
Peptide Backbone ◽  
Practical Advantage ◽  
The Past ◽  
Naturally Occurring ◽  
Atom Source ◽  
Photonic Energy

AbstractThe visible light induced, photocatalysts or photoabsorbing EDA complexes mediated cleavage of pyridinium C-N bond were reported in the past years. Here, we report an ionic compound promote homolytic cleavage of pyridinium C-N bond by exploiting the photonic energy from visible light. This finding is successfully applied in deaminative hydroalkylation of a series of alkenes including naturally occurring dehydroalanine, which provides an efficient way to prepare β-alkyl substituted unnatural amino acids under mild and photocatalyst-free conditions. Importantly, by using this protocol, the deaminative cyclization of peptide backbone N-terminals is realized. Furthermore, the use of Et3N or PPh3 as reductants and H2O as hydrogen atom source is a practical advantage. We anticipate that our protocol will be useful in peptide synthesis and modern peptide drug discovery.

Imine as a Linchpin Approach for Distal C(sp2)–H Functionalization

2020 ◽  
Author(s):  
Sukdev Bag ◽  
Sadhan Jana ◽  
Sukumar Pradhan ◽  
Suman Bhowmick ◽  
Nupur Goswami ◽  
...  
Keyword(s):  
Organic Molecules ◽  
Bond Activation ◽  
Bond Formation ◽  
Ancillary Ligand ◽  
Significant Challenge ◽  
Site Selectivity ◽  
Directing Group ◽  
Covalently Linked ◽  
Complex Organic ◽  
Post Functionalization

<p>Despite the widespread applications of C–H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing group (DG) served as an ancillary ligand to ensure proximal <i>ortho</i>-, distal <i>meta</i>- and <i>para</i>-C-H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C–H functionalization: introduction of DG prior to C–H activation and removal of DG post-functionalization. We introduce here a transient directing group for distal C(<i>sp<sup>2</sup></i>)-H functionalization <i>via</i> reversible imine formation. By overruling facile proximal C-H bond activation by imine-<i>N</i> atom, a suitably designed pyrimidine-based transient directing group (TDG) successfully delivered selective distal C-C bond formation. Application of this transient directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the distal position has been explored.</p>

Carbon Dioxide-Mediated C(sp2)–H Arylation of Primary and Secondary Benzylamines

2018 ◽  
Author(s):  
Mohit Kapoor ◽  
Pratibha Chand-Thakuri ◽  
Michael Young
Keyword(s):  
Carbon Dioxide ◽  
Transition Metal ◽  
Bond Activation ◽  
Bond Formation ◽  
Carbon Bond ◽  
Chelate Effect ◽  
Free Amine ◽  
Carbon Carbon Bond ◽  
New Strategy ◽  
Metal Catalyzed

Carbon-carbon bond formation by transition metal-catalyzed C–H activation has become an important strategy to fabricate new bonds in a rapid fashion. Despite the pharmacological importance of <i>ortho</i>-arylbenzylamines, however, effective <i>ortho</i>-C–C bond formation from C–H bond activation of free primary and secondary benzylamines using Pd<sup>II</sup> remains an outstanding challenge. Presented herein is a new strategy for constructing <i>ortho</i>-arylated primary and secondary benzylamines mediated by carbon dioxide (CO<sub>2</sub>). The use of CO<sub>2</sub> is critical to allowing this transformation to proceed under milder conditions than previously reported, and that are necessary to furnish free amine products that can be directly used or elaborated without the need for deprotection. In cases where diarylation is possible, a chelate effect is demonstrated to facilitate selective monoarylation.

Synthesis of Drugs and Biorelevant N-heterocycles Employing Recent Advances in C-N Bond Formation

2020 ◽  
Vol 24 (20) ◽  
pp. 2293-2340
Author(s):  
Firdoos Ahmad Sofi ◽  
Prasad V. Bharatam
Keyword(s):  
Kinase Inhibitors ◽  
Bond Formation ◽  
Comprehensive Review ◽  
Biologically Relevant ◽  
Lead Compounds ◽  
Heterocyclic Molecules ◽  
The Past ◽  
Anti Cancer ◽  
Modern Methods ◽  
Bond Formation Reactions

C-N bond formation is a particularly important step in the generation of many biologically relevant heterocyclic molecules. Several methods have been reported for this purpose over the past few decades. Well-known named reactions like Ullmann-Goldberg coupling, Buchwald-Hartwig coupling and Chan-Lam coupling are associated with the C-N bond formation reactions. Several reviews covering this topic have already been published. However, no comprehensive review covering the synthesis of drugs/ lead compounds using the C-N bond formation reactions was reported. In this review, we cover many modern methods of the C-N bond formation reactions, with special emphasis on metal-free and green chemistry methods. We also report specific strategies adopted for the synthesis of drugs, which involve the C-N bond formation reactions. Examples include anti-cancer, antidepressant, anti-inflammatory, anti-atherosclerotic, anti-histaminic, antibiotics, antibacterial, anti-rheumatic, antiepileptic and anti-diabetic agents. Many recently developed lead compounds generated using the C-N bond formation reactions are also covered in this review. Examples include MAP kinase inhibitors, TRKs inhibitors, Polo-like Kinase inhibitors and MPS1 inhibitors.

Formation of Carbon-Oxygen Bond Mediated by Hypervalent Iodine Reagents Under Metal-free Conditions

2020 ◽  
Vol 17 ◽  
Author(s):  
Ayesha Jalil ◽  
Yaxin O Yang ◽  
Zhendong Chen ◽  
Rongxuan Jia ◽  
Tianhao Bi ◽  
...  
Keyword(s):  
Natural Products ◽  
Bond Formation ◽  
Building Blocks ◽  
Review Article ◽  
Hypervalent Iodine ◽  
Metal Free ◽  
Bioactive Natural Products ◽  
The Past ◽  
Oxygen Bond ◽  
Privileged Scaffolds

: Hypervalent iodine reagents are a class of non-metallic oxidants have been widely used in the construction of several sorts of bond formations. This surging interest in hypervalent iodine reagents is essentially due to their very useful oxidizing properties, combined with their benign environmental character and commercial availability from the past few decades ago. Furthermore, these hypervalent iodine reagents have been used in the construction of many significant building blocks and privileged scaffolds of bioactive natural products. The purpose of writing this review article is to explore all the transformations in which carbon-oxygen bond formation occurred by using hypervalent iodine reagents under metal-free conditions

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