An excellent reagent for the removal of the t-butyldimethylsilyl protecting group

Newton, Roger F.; Reynolds, Derek P.; Finch, Mark A. W.; Kelly, David R.; Roberts, Stanley M.

doi:10.1016/s0040-4039(01)86482-0

Cited by 212 publications

(65 citation statements)

References 6 publications

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“…Fortunately, treatment of 104 with hydrofluoric acid in acetonitrile 36 gave a much better result (95% yield), and 26 was easily converted into various heteroaryl ether targets (27, 29-31) via sodium hydride-catalysed S N Ar reactions on the haloheterocycles 105-108. 37 The isomeric pyridine 28 was also obtained in moderate yield (25%) by reaction of 6-(trifluoromethyl)pyridin-3-ol and sodium hydride with the known 30 epoxide 109 (Scheme 2D).…”

Section: Vl Is Caused By Leishmania Donovani (L Don) and Leishmania mentioning

confidence: 99%

Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis

et al. 2016

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Phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of DNDI-VL-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (VL). Additional work was then conducted to delineate its essential structural features, aiming to improve solubility and safety without compromising activity against VL. While the 4-nitroimidazole portion was specifically required, several modifications to the aryloxy side chain were well tolerated e.g., exchange of the linking oxygen for nitrogen (or piperazine), biaryl extension, and replacement of phenyl rings by pyridine. Several less lipophilic analogues displayed improved aqueous solubility, particularly at low pH, although stability towards liver microsomes was highly variable.Upon evaluation in a mouse model of acute Leishmania donovani infection, one phenylpyridine derivative (37) stood out, providing efficacy surpassing that of the original preclinical lead.3

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Section: Vl Is Caused By Leishmania Donovani (L Don) and Leishmania mentioning

confidence: 99%

Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis

et al. 2016

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“…Finally, the tertbutylsilane fragment involved in the compound 10 was removed with hydrofluoric acid (vii) to form 11 A B TIME (min) Finally, the fifth stage was performed by the removal of the tert-butyldimethylsilyl of 10 to form the compound 11 (Fig. 5); it is important to mention that several reagents have been used to remove the protector groups such as dimethylaluminum chloride [34], palladium(II) [35], and hydrofluoric acid [36]. In this study, aqueous hydrofluoric acid was used to remove the tert-butyldimethylsilyl group.…”

Section: Results and Discussion Evaluation Chemistrymentioning

confidence: 99%

Design and synthesis of a new steroid-macrocyclic derivative with biological activity

et al. 2017

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The aims of this study were to evaluate the positive inotropic effect of a new macrocyclic derivative (compound 11) and characterize the molecular mechanism involved in its biological activity. The first step was achieved by synthesis of a macrocyclic derivative involving a series of reactions for the preparation of several steroid derivatives such as (a) steroidpyrimidinone (3 and 4), (b) steroid-amino (5), (c) steroidimino (6), (d) ester-steroid (7 and 8), and (e) amido-steroid (9 and 10). Finally, 11 was prepared by removing the tertbutyldimethylsilane fragment of 10. The biological activity of compounds on perfusion pressure and vascular resistance was evaluated on isolated rat heart using the Langendorff model. The inotropic activity of 11 was evaluated in presence of prazosin, metoprolol, indomethacin, nifedipine, and flutamide to characterize its molecular mechanism. Theoretical experiments were carried out with a Docking model, to assess potential interactions of androgen receptor with 11. The results showed that only this macrocyclic derivative exerts changes on perfusion pressure and vascular resistance translated as the positive inotropic effect, and this effect was blocked with flutamide; these data indicate that the positive inotropic activity induced by this macrocyclic derivative was via androgen receptor activation. The theoretical results indicated that the interaction of the macrocyclic derivative with the androgen receptor involves several amino acid residues such as Leu 704 , Asn 705 , Met 780 , Cys 784 , Met 749 , Leu 762 , Phe 764 , Ser 778 , and Met 787 . In conclusion, all these data suggest that the positive inotropic activity of the macrocyclic derivative may depend on its chemical structure.

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“…In this reaction, 4-dimethylaminopyridine (DMAP) was used as a catalyst and N,N′-dicyclohexylcarbodiimide (DCC) as a dehydration agent [13] . Finally, the deprotection reaction of 4 in 5% HF [14] aqueous solution gave the desired 5α,14α-cevanin-6-O-20β-hydroxy-3β-yl-3α,7α,12α-trihydroxy-5β-cholan-24-oate, 5. The chemoselective esterification reaction of 3 with verticinone in CH 2 Cl 2 provided 4 in 58.9% yield.…”

Section: Methodsmentioning

confidence: 99%

Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor

et al. 2009

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Aim:The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Ver showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver. Methods: Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver's central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver's addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. Results: The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver, suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response. Conclusion: These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.

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An excellent reagent for the removal of the t-butyldimethylsilyl protecting group

Cited by 212 publications

References 6 publications

Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis

Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis

Design and synthesis of a new steroid-macrocyclic derivative with biological activity

Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor

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