Debenzylation using catalytic hydrogenolysis in trifluoroethanol, and the total synthesis of (−)-raumacline

Bailey, Patrick D.; Beard, Mark A.; Dang, Hoa P.T.; Phillips, Theresa R.; Price, Richard A.; Whittaker, James H.

doi:10.1016/j.tetlet.2008.01.104

Cited by 27 publications

(27 citation statements)

References 8 publications

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“…We found that more catalyst (10% Pd/C, 1:1 w / w ) and longer reaction time (4 days, 50 psi H 2 ) increased the amount of 11 to 50%. It was reported that N -methylation was observed in hydrogenolysis of benzyl group in an alkaloid synthesis (40–42). The proposed mechanism is that the catalyst of palladium (40) or other precious metals such as ruthenium (43) and iridium (44) can oxidize the adsorbed alcohol to the corresponding aldehyde, which can be trapped by free amine and then be reduced by hydrogen to N -alkylated products.…”

Section: Resultsmentioning

confidence: 99%

Bisethylnorspermine Lipopolyamine as Potential Delivery Vector for Combination Drug/Gene Anticancer Therapies

Dong

et al. 2010

Pharm Res

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Purpose To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. Methods Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. Results Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3–4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low µM range, falls within a relevant and typical concentration range required for efficient gene delivery. Conclusions These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer.

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Section: Resultsmentioning

confidence: 99%

Bisethylnorspermine Lipopolyamine as Potential Delivery Vector for Combination Drug/Gene Anticancer Therapies

Dong

et al. 2010

Pharm Res

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“…Stereochemistry of compounds 3a-f was confirmed by spectroscopic analysis [17,18]; e.g. 3e gave a doublet of doublets at À125.74 ppm (dd, 2 J F-P = 105.4, 3 J F-H = 40.1 Hz) in 19 F NMR spectra. The observed 3 J F-H = 40.1 Hz coupling constant is The next step in the synthesis was simultaneous hydrogenation of the double bond and removal of benzyl protecting groups (Scheme 2).…”

Section: Resultsmentioning

confidence: 92%

“…Unfortunately, we did not observe formation of the expected products. Next, we have decided to adapt the methodology of hydrogenation proposed by Whittaker, using trifluoroethanol (TFE) as a solvent [19]. Comparing to Whittaker method we increased the amount of the catalyst to 20% (v/v) and extended the reaction time to 3 days (Table 1, entry 7).…”

Section: Resultsmentioning

confidence: 99%

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Preparation and characterization of α-fluorinated-γ-aminophosphonates

Kaźmierczak

Kubicki

Koroniak

2014

Journal of Fluorine Chemistry

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“…The hydrogenolysis condition set the primary amine on 6′ position free for further guanidylation. Trifluoroethanol was used as solvent to avoid N -alkylation in alcoholic solvent [58]. At last, global deprotection of base-labile blocking groups in the present of lithium hydroxide, followed by acidic removal of t -butoxycarbonyl completed the synthesis of the target compound GMS (Refer to the Supporting Methods for the detailed synthesis method).…”

Section: Resultsmentioning

confidence: 99%

Structural basis of arginine asymmetrical dimethylation by PRMT6

Zheng

Eram

et al. 2016

Biochemical Journal

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PRMT6 is a type I protein arginine methyltransferase, generating the asymmetric dimethylarginine mark on proteins such as histone H3R2. Asymmetric dimethylation of histone H3R2 by PRMT6 acts as a repressive mark that antagonizes trimethylation of H3 lysine 4 by the MLL histone H3K4 methyltransferase. PRMT6 is overexpressed in several cancer types, including prostate, bladder and lung cancers; therefore, it is of great interest to develop potent and selective inhibitors for PRMT6. Here we report the synthesis of a potent bi-substrate inhibitor GMS (6′-methyleneamine sinefungin, an analogue of sinefungin), and the crystal structures of human PRMT6 in complex respectively with SAH and the bi-substrate inhibitor GMS that shed light on the significantly improved inhibition effect of GMS on methylation activity of PRMT6 compared to SAH and a SAM competitive methyltransferase inhibitor sinefungin (SNF). In addition, we also crystallized PRMT6 in complex with SAH and a short arginine containing peptide. Based on the structural information here and available in the PDB database, we propose a mechanism that can rationalize the distinctive arginine methylation product specificity of different types of arginine methyltransferases and pinpoint the structural determinant of such a specificity.

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Debenzylation using catalytic hydrogenolysis in trifluoroethanol, and the total synthesis of (−)-raumacline

Cited by 27 publications

References 8 publications

Bisethylnorspermine Lipopolyamine as Potential Delivery Vector for Combination Drug/Gene Anticancer Therapies

Bisethylnorspermine Lipopolyamine as Potential Delivery Vector for Combination Drug/Gene Anticancer Therapies

Preparation and characterization of α-fluorinated-γ-aminophosphonates

Structural basis of arginine asymmetrical dimethylation by PRMT6

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