Synthesis and reductive desulfurization of chiral non-racemic benzothienoindolizines. An efficient approach to a novel bioactive tylophorine alkaloid analogue and 6-phenylindolizidine

Šafář, Peter; Žúžiová, Jozefína; Bobošíková, Mária; Marchalı́n, Štefan; Prónayová, Nadežda; Comesse, Sébastien; Daı̈ch, Adam

doi:10.1016/j.tetasy.2009.08.010

Cited by 18 publications

(1 citation statement)

References 48 publications

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“…HSQC and HMBC techniques Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 5/27/15 3:06 PM were used throughout the study for the assignment of the 1 H-13 C relationships. Preparation of compounds I-IV, VIII-XV, XVIII-XXI from L-glutamic acid was introduced in our previous papers (Marchalin et al, 1999(Marchalin et al, , 1993Šafář et al, 2009a, 2009b.…”

Section: Synthesis Of Indolizinesmentioning

confidence: 99%

Newly synthesized indolizine derivatives – antimicrobial and antimutagenic properties

Olejníková¹,

Bírošová²,

Švorc

et al. 2015

Chemical Papers

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A series of indolizine derivatives have been synthesized and subjected to antibacterial screening studies. Antibacterial activity of 21 derivatives was investigated against Staphylococcus aureus, Mycobacterium smegmatis, Salmonella typhimurium and Escherichia coli; also, the sensitivity of model yeast Candida parapsilosis and some model filamentous fungi Aspergillus fumigatus, Alternaria alternata, Botrytis cinerea and Microsporum gypseum was tested. Newly synthesized indolizine derivatives have shown selective toxicity to Gram-positive bacteria S. aureus and were also considered to be able to inhibit the acidoresistant rod M. smegmatis. Derivative XXI has shown the highest inhibition effect with the bacteriostatic effect on the cells at the concentration of 25 µg mL −1 . The best antifungal activity has been detected in the presence of derivative XIII. Derivative XIII did also affect the morphology of hyphal tips of B. cinerea, which led to enhanced ramification of hyphae. Finally, the antimutagenic activity of derivatives was investigated. Significant antimutagenic activity was registered in case of derivative VIII. The number of induced revertants by mutagen [2-(5-nitrofuryl)acrylic acid] was decreased almost to the level of spontaneous revertants in the lowest applied concentration (50 µg per plate).

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Section: Synthesis Of Indolizinesmentioning

confidence: 99%

Newly synthesized indolizine derivatives – antimicrobial and antimutagenic properties

Olejníková¹,

Bírošová²,

Švorc

et al. 2015

Chemical Papers

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Asymmetric Synthesis and Binding Study of New Long‐Chain HPA‐12 Analogues as Potent Ligands of the Ceramide Transfer Protein CERT

Ďuriš

Daı̈ch

Santos

et al. 2016

Chemistry A European J

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A series of 12 analogues of the Cer transfer protein (CERT) antagonist HPA-12 with long aliphatic chains were prepared as their (1R,3S)-syn and (1R,3R)-anti stereoisomers from pivotal chiral oxoamino acids. The enantioselective access to these intermediates as well as their ensuing transformation relied on a practical crystallization-induced asymmetric transformation (CIAT) process. Sonogashira coupling followed by triple bond reduction and thiophene ring hydrodesulfurization (HDS) into the corresponding alkane moieties was then implemented to complete the synthetic routes delivering the targeted HPA-12 analogues in concise 4- to 6-step reaction sequences. Ten compounds were evaluated regarding their ability to bind to the CERT START domain by using the recently developed time-resolved FRET-based homogeneous (HTR-FRET) binding assay. The introduction of a lipophilic appendage on the phenyl moiety led to an overall 10- to 1000-fold enhancement of the protein binding, with the highest effect being observed for a n-hexyl residue in the meta position. The importance of the phenyl ring for the activity was indicated by the reduced potency of the 3-deoxyphytoceramide aliphatic analogues. The 1,3-syn stereoisomers were systematically more potent than their 1,3-anti analogues. In silico studies were used to rationalized these trends, leading to a model of protein recognition coherent with the stronger binding of (1R,3S)-syn HPAs.

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Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts

et al. 2012

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Six novel enantiopure epimeric indolizidinediols have been easily prepared in high yields by an effective and well‐established regioselective THF ring‐opening reaction as a key step. Quarternization of these species was also studied and comparison was made to the quaternizations of other substituted indolizidines. Importantly, a combined theoretical DFT‐QTAIM study has cast light on the various factors that explain the observed conformational selectivity. The inhibitory properties of the six synthesized indolizidines were then investigated against the recombinant Golgi α‐mannosidase‐IIb (dGMIIb) and lysosomal α‐mannosidase (dLM408), human homologues of Drosophila melanogaster. Among the tested compounds, two of them, 4a and 4b, exhibited a pH‐dependent inhibition of dGMIIb at the milimolar level (IC50 = 3.5 or 1.7 mM at pH 5.8 or 6.5, respectively) without affecting the activity of dLM408.

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Synthesis and reductive desulfurization of chiral non-racemic benzothienoindolizines. An efficient approach to a novel bioactive tylophorine alkaloid analogue and 6-phenylindolizidine

Cited by 18 publications

References 48 publications

Newly synthesized indolizine derivatives – antimicrobial and antimutagenic properties

Newly synthesized indolizine derivatives – antimicrobial and antimutagenic properties

Asymmetric Synthesis and Binding Study of New Long‐Chain HPA‐12 Analogues as Potent Ligands of the Ceramide Transfer Protein CERT

Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts

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