Total Synthesis of the Marine Alkaloid Halichlorine: Development and Use of a General Route to Chiral Piperidines

Liu, Dazhan; Acharya, Hukum P.; Yu, Maolin; Wang, Jian; Yeh, Vince S. C.; Kang, Shunzhen; Chiruta, Chandramouli; Jachak, Santosh M.; Clive, Derrick L. J.

doi:10.1021/jo901481n

Cited by 44 publications

(24 citation statements)

References 92 publications

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“…Firstly, inhibiting the interaction of superantigens with the T cell receptor and MHC II has been explored by using peptide mimetics of superantigens [35,36], protein chimeras of the binding sites of superantigens [37], and nucleic acid aptamers which specifically bind superantigens [38]. Secondly, inhibitors have been developed against the key mediators of pro-inflammatory intracellular signaling pathways or pro-inflammatory cytokines and chemokines themselves [39-44]. Some of the experimental therapeutics have been previously approved by the FDA for other indications, receiving particular attention especially for biodefence purposes (e.g.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome

et al. 2014

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BackgroundToxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS.MethodsEffects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 μg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 μg) in HLA-DR4 transgenic mice.ResultsDespite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS.ConclusionsOur results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than IL-2, IL-6 and TNF are likely to play critical mechanistic roles in the pathogenesis of experimental TSS.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome

et al. 2014

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“…[142] Chain termini were differentiated by a two-component, domino cyclisation sequence to generate 41. Further manipulation intercepted an intermediate from Clive and coworkers's earlier approach, [143] thereby completing a formal total synthesis.…”

Section: Independent Reactionsmentioning

confidence: 99%

Multi-Bond Forming Processes in Efficient Synthesis

Green¹,

Sherburn²

2013

Aust. J. Chem.

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An increasing number of synthetic organic chemists are embracing the philosophy of efficiency. Herein we highlight multi-bond forming processes, which form two or more new covalent bonds in a single synthetic operation. Such processes, which have the ability to rapidly increase structural complexity, are preeminent in contemporary synthetic organic chemistry. In this short review we classify, analyse, and contrast contemporary multi-bond forming processes, frame these cutting edge contributions within a historical context, and speculate on likely future developments in the area.

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“…In the synthesis of the marine alkaloid halichlorine, Clive preformed the five‐membered ring through a reductive 5‐ exo ‐ trig radical cyclization from quinolizidine 140 en route to unsaturated lactam 141 (Scheme b).…”

Section: From Calchogen Derivativesmentioning

confidence: 99%

Radical Reactions in Alkaloid Synthesis: A Perspective from Carbon Radical Precursors

Bonjoch

Diaba

2020

Eur J Org Chem

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The usefulness of radical reactions in alkaloid synthesis is reviewed from the perspective of the functional groups embedded in the molecular structure of synthetic intermediates, that act as precursors of carbon‐centered radicals in the construction of new C–C bonds. The functional groups featured are alkenes, alkynes, halides (alkyl, vinyl, aryl), xanthates, sulfides, selenides, aldehydes, ketones, carboxylic acid derivatives (selenoesters, haloacetamides), β‐dicarbonyl compounds, and α‐heterosubstituted nitrogen‐compounds. The use of nitrogen‐centered radicals for C–N bond formation is also covered. Among the variety of radical processes applied, the most predominant are the hydride reductive method (Sn, Si), atom transfer radical reactions (Cu, Ru, B), and single‐electron transfer radical reactions promoted by Sm, Ni, Fe, Mn, Ti, and Ag. This review showcases the role radical reactions have played in the recent development of new strategies in alkaloid synthesis, as well as the implementation of new radical procedures in demanding substrates.

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Total Synthesis of the Marine Alkaloid Halichlorine: Development and Use of a General Route to Chiral Piperidines

Cited by 44 publications

References 92 publications

Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome

Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome

Multi-Bond Forming Processes in Efficient Synthesis

Radical Reactions in Alkaloid Synthesis: A Perspective from Carbon Radical Precursors

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