Total Synthesis of Polydiscamides B, C, and D via a Convergent Native Chemical Ligation–Oxidation Strategy

Santhakumar, Gajan; Payne, Richard J.

doi:10.1021/ol502045u

Cited by 15 publications

(15 citation statements)

References 21 publications

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“…Different conditions for this transformation were screened ( Scheme 3 B). 28 , 29 Fortunately, the thioether oxidized smoothly within a few hours in oxone/HOAc/NaOAc to produce sulfonic acid 41 in 70% yield.…”

Section: Resultsmentioning

confidence: 99%

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury

Cui

Zhang

et al. 2022

J. Med. Chem.

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure–activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

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Section: Resultsmentioning

confidence: 99%

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury

Cui

Zhang

et al. 2022

J. Med. Chem.

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“…), 644,645 polydiscamides B-D (Ircinia sp. ), 646,647 callipeltin M (Latrunculia sp. ), 648,649 topsentolide A2 (revised 1035, Topsentia sp.…”

Section: Spongesmentioning

confidence: 99%

Marine natural products

et al. 2016

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This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

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“…Moreover, in some cases, a mixed solid-phase/solution synthesis strategy is employed to accomplish total synthesis of the cyclopolypeptide [132], e.g., during the total synthesis of the naturally-occurring proline-rich cyclic octapeptide stylissamide X, the linear octapeptide was assembled first by standard Fmoc solid-phase peptide synthesis (SPPS), and cyclization was carried out subsequently by the solution method. Total synthesis can also be achieved via a convergent native chemical ligation-oxidation strategy [133], e.g., polydiscamides B–D, or utilizing diethyl phosphorocyanidate/BOP-Cl chemistry [134], e.g., axinastatins 2 and 3.…”

Section: Chemistrymentioning

confidence: 99%

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

et al. 2016

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Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.

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Total Synthesis of Polydiscamides B, C, and D via a Convergent Native Chemical Ligation–Oxidation Strategy

Cited by 15 publications

References 21 publications

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury

Marine natural products

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

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