Total Synthesis and Antibacterial Investigation of Plusbacin A<sub>3</sub>

Katsuyama, Akira; Paudel, Atmika; Panthee, Suresh; Hamamoto, Hiroshi; Kawakami, Toru; Hojo, Hironobu; Yakushiji, Fumika; Ichikawa, Satoshi

doi:10.1021/acs.orglett.7b01629

Cited by 23 publications

(25 citation statements)

References 29 publications

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“…The key intermediates were synthesized efficiently by this method (Scheme 30). 43,118 Cyclic Imines via Fischer Indole Synthesis. Compounds containing indole moiety exist in many natural products and bioactive compounds.…”

Section: ■ Introductionmentioning

confidence: 99%

Cyclic Imines in Ugi and Ugi-Type Reactions

et al. 2020

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Ugi four-component reactions (U-4CRs) are widely recognized as being highly efficient for the synthesis of pseudopeptides. However, the products of these reactions are not so interesting as drug candidates because they are not conformationally restricted enough for a potent interaction with biological targets. One possible way to overcome this problem is to replace amine and oxo components in the U-4CRs with cyclic imines in so-called Joullié−Ugi three-component reactions (JU-3CRs). This approach provides a robust single-step route to peptide moieties connected to N-heterocyclic motifs that are found as core skeletons in many natural products and pharmaceutical compounds. JU-3CRs also provide much better diastereoselectivity than their four-component analogues. We survey here the redesign of many synthetic routes for the efficient preparation of a wide variety of three-, five-, six-, and seven-membered heterocyclic compounds connected to the peptide backbone. Additionally, in the Ugi reactions based on the cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids, respectively, leading to the synthesis of N-heterocycles attached to oxazoles or tetrazoles, which are of great pharmaceutical significance. This Review includes all research articles related to Ugi reactions based on the cyclic imines to the year 2020 and will be useful to chemists in designing novel synthetic routes for the synthesis of individual and combinatorial libraries of natural products and drug-like compounds.

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Section: ■ Introductionmentioning

confidence: 99%

Cyclic Imines in Ugi and Ugi-Type Reactions

et al. 2020

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“…Recently, the total synthesis of plusbacin A 3 69 was achieved via a solvent-dependent diastereodivergent Joullié−Ugi three-component reaction (JU-3CR) (Scheme 11). 55 At first, VanNieuwenhze and his research team in 2007 performed the total synthesis of 69 through a conventional peptide coupling starting from trans-Pro-(3-OH). 56 Yoshida and co-workers had isolated plusbacin A 3 in 1992 from the culture broth of Pseudomonas sp.…”

Section: Syntheses Based On the Ugi Reactionmentioning

confidence: 99%

Application of multicomponent reactions in the total synthesis of natural peptides

Ziarani¹,

Moradi²,

Mahammadkhani³

2019

Arkivoc

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Multicomponent reactions (MCRs) have been widely applied for the synthesis of biologically active molecules with high complexity and diversity. Nowadays, total synthesis of natural peptides, due to their multifarious application areas, has attracted much attention of organic chemists. MCRs are a powerful and efficient method for the production of natural peptides in a limited number of steps. This review presents an overview on application of multicomponent reactions as a key step in the synthesis of natural peptides.

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“…Many guanidine secondary metabolites isolated from microorganisms, plants, and animals exhibit interesting biological activity . For example, plusbacin A 3 , empedopeptin, and tripropeptin C are bacterially produced cyclic lipodepsipeptides that share, among other common structural features, a characteristic arginine residue . These compounds exhibit potent antimicrobial activity against a wide range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). − Synthetic guanidinium-containing compounds (including small peptides and peptidomimetics) comprise promising drug leads that target bacterial and viral infections, and diseases in the central nervous system or have potential therapeutic applications e.g., as anti-inflammatory, antidiabetic, or anticancer agents .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of 1H-Triazole-1-[N,N′-Bis(tert-butoxycarbonyl)]carboxamidine in Solution-Phase and On-Resin Guanidinylation

2021

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Several guanidines and guanidinylated peptides have substantial potential as therapeutics, but efficient guanidinylation reagents are vital for easy access to these compounds. Presently, pyrazole-1-carboxamidine type reagents are commonly used in the transformations of amines into corresponding guanidines. Here, we report a comparative study of the utility of 1H-triazole-1-[N,N′-bis(tert-butoxycarbonyl)]carboxamidine, which was synthesized in two steps and readily upscaled to gram amounts. It exhibited excellent performance in solution-phase reactions, rapidly converting a set of representative aliphatic primary and unhindered secondary amines as well as aniline into the corresponding bis(tert-butoxycarbonyl)-protected guanidines. To enable a direct assessment of the reactivity of guanidinylation reagents, conversions were performed in deuterated solvents (d 7-DMF or d 8-THF), allowing for continuous analysis of the reaction mixtures by 1H and 13C NMR. Likewise, 1H-triazole-1-[N,N′-bis(tert-butoxycarbonyl)]carboxamidine proved to be a versatile reagent in solid-phase conversions, for example, a resin-bound test peptide (KFFKFFK) was fully guanidinylated in only 2 h by using 2 equivalents of the reagent per free amino group. Also, 1H-triazole-1-[N,N′-bis(tert-butoxycarbonyl)]carboxamidine proved capable of completely guanidinylating more sterically hindered N-terminal residues (e.g., N-methyl amino acids or a peptoid) in resin-bound peptides. Its superior reactivity and stability demonstrated under heating conditions make 1H-triazole-1-[N,N′-bis(tert-butoxycarbonyl)]carboxamidine a valuable guanidinylation reagent both in solution- and solid-phase synthesis.

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Total Synthesis and Antibacterial Investigation of Plusbacin A₃

Cited by 23 publications

References 29 publications

Cyclic Imines in Ugi and Ugi-Type Reactions

Cyclic Imines in Ugi and Ugi-Type Reactions

Application of multicomponent reactions in the total synthesis of natural peptides

Evaluation of 1H-Triazole-1-[N,N′-Bis(tert-butoxycarbonyl)]carboxamidine in Solution-Phase and On-Resin Guanidinylation

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Total Synthesis and Antibacterial Investigation of Plusbacin A3

Cited by 23 publications

References 29 publications

Cyclic Imines in Ugi and Ugi-Type Reactions

Cyclic Imines in Ugi and Ugi-Type Reactions

Application of multicomponent reactions in the total synthesis of natural peptides

Evaluation of 1H-Triazole-1-[N,N′-Bis(tert-butoxycarbonyl)]carboxamidine in Solution-Phase and On-Resin Guanidinylation

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Product

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Total Synthesis and Antibacterial Investigation of Plusbacin A₃