A divergent route to 9,10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: synthesis of (±)-isocorypalmine and oxypalmatine

Gadhiya, Satishkumar; Ponnala, Shashikanth; Harding, Wayne W.

doi:10.1016/j.tet.2015.01.004

Cited by 25 publications

(14 citation statements)

References 32 publications

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“…Based on the above spectroscopic properties, 1 was characterized as a new 8-oxoprotoberberine alkaloid with the structure 2,10-dihydroxy-3,9-dimethoxy-5,6-dihydro-8 H -isoquinolino[3,2-a]isoquinolin-8-one, and given the trivial name huberanthine A. It should be noted that this chemical structure has been mentioned as an in situ intermediate for the organic synthesis of oxypalmatine [ 16 ]. However, so far no chemical, physical, or spectroscopic properties of 1 have been described.…”

Section: Resultsmentioning

confidence: 99%

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Constituents of Huberantha jenkinsii and Their Biological Activities

et al. 2020

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The phytochemical investigation of Huberantha jenkinsii resulted in the isolation of two new and five known compounds. The new compounds were characterized as undescribed 8-oxoprotoberberine alkaloids and named huberanthines A and B, whereas the known compounds were identified as allantoin, oxylopinine, N-trans-feruloyl tyramine, N-trans-p-coumaroyl tyramine, and mangiferin. The structure determination was accomplished by spectroscopic methods. To evaluate therapeutic potential in diabetes and Parkinson’s disease, the isolates were subjected to assays for their α-glucosidase inhibitory activity, cellular glucose uptake stimulatory activity, and protective activity against neurotoxicity induced by 6-hydroxydopamine (6-OHDA). The results suggested that mangiferin was the most promising lead compound, demonstrating significant activity in all the test systems.

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Section: Resultsmentioning

confidence: 99%

“…6-OHDA was dissolved in 0.02% ascorbic acid in the same medium to prevent the degradation of 6-OHDA. The toxic dose of 6-OHDA was determined by preliminary screening at different concentrations after 2 h incubation of SH-SY5Y cells at 37 • C under 5% CO 2 [15,16].…”

Section: Assay For Neuroprotective Activitymentioning

confidence: 99%

Constituents of Huberantha jenkinsii and Their Biological Activities

et al. 2020

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“…35 This route is depicted in Scheme 1. Commercially available phenol 2 was reacted with ethoxymethyl chloride.…”

Section: Resultsmentioning

confidence: 99%

Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity

Gadhiya

Madapa

Kurtzman

et al. 2016

Bioorganic & Medicinal Chemistry

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Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that a) contain various alkoxy substituents at the C10 position and, b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on D3 and σ2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and σ2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for σ2 receptors as well as σ2 versus σ1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and σ receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds.

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“…The precision medicine platform is also being leveraged to deliver point-of-care diagnosis in patients. As an example, emphasis is now on querying the BALFosome (broncheoalveolar lavage fluid) in patients presenting with acute respiratory distress or urine transcriptome or proteome in patients presenting with acute kidney disease or NS [ 27 , 28 , 29 ]. Use of a minimally invasive or non-invasive omics query strategy spares the patient pain and/or distress and provides valuable information that can be acquired relatively rapidly, enabling enrollment or exclusion of the patient.…”

Section: Precision Medicinementioning

confidence: 99%

Deep Learning in Drug Discovery and Medicine; Scratching the Surface

et al. 2018

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The practice of medicine is ever evolving. Diagnosing disease, which is often the first step in a cure, has seen a sea change from the discerning hands of the neighborhood physician to the use of sophisticated machines to use of information gleaned from biomarkers obtained by the most minimally invasive of means. The last 100 or so years have borne witness to the enormous success story of allopathy, a practice that found favor over earlier practices of medical purgatory and homeopathy. Nevertheless, failures of this approach coupled with the omics and bioinformatics revolution spurred precision medicine, a platform wherein the molecular profile of an individual patient drives the selection of therapy. Indeed, precision medicine-based therapies that first found their place in oncology are rapidly finding uses in autoimmune, renal and other diseases. More recently a new renaissance that is shaping everyday life is making its way into healthcare. Drug discovery and medicine that started with Ayurveda in India are now benefiting from an altogether different artificial intelligence (AI)—one which is automating the invention of new chemical entities and the mining of large databases in health-privacy-protected vaults. Indeed, disciplines as diverse as language, neurophysiology, chemistry, toxicology, biostatistics, medicine and computing have come together to harness algorithms based on transfer learning and recurrent neural networks to design novel drug candidates, a priori inform on their safety, metabolism and clearance, and engineer their delivery but only on demand, all the while cataloging and comparing omics signatures across traditionally classified diseases to enable basket treatment strategies. This review highlights inroads made and being made in directed-drug design and molecular therapy.

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A divergent route to 9,10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: synthesis of (±)-isocorypalmine and oxypalmatine

Cited by 25 publications

References 32 publications

Constituents of Huberantha jenkinsii and Their Biological Activities

Constituents of Huberantha jenkinsii and Their Biological Activities

Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity

Deep Learning in Drug Discovery and Medicine; Scratching the Surface

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