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1.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(8):707-732
Results are reported on the regioselective C‐deuteriation of 2‐methyl‐tetralone using a series of D‐sources and tertiary amines as potential mediators. The results presented further aid the understanding of kinetic deuteriation of both ‘base‐containing’ and ‘base‐free’ enolates. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
2.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(7):641-652
Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro‐base in the presence of a suitable deuterium donor. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
3.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(6):359-371
Results are reported on the regioselective C‐deuteriation of 2‐methyl tetralone using piperidine‐d11 as a deuterium source. The results presented further aid the understanding of kinetic deuteriation of amine–enolate complexes. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
4.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(5):337-352
Results are reported on the regioselective C‐deuteriation of a series of enol acetates (derived from the aryl alkyl ketones) using molecular deuterium as the D‐source and palladium‐on‐barium sulphate as the mediator. The results presented highlight potential problems associated with the deuteriation of enol acetates. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
5.
Acetyl cedrene and its follower. An Isotopic,NMR and MS Structure elucidation and deuteriation study
Fadhil S. Kamounah Peter Christensen Poul Erik Hansen 《Journal of labelled compounds & radiopharmaceuticals》2011,54(3):126-131
Acetylation of cedarwood oil (Virginia) leads besides acetyl cedrene also to a minor product, 1,7,7‐trimethyl‐2,3‐(3′,4′‐dimethylbenzo)bicyclo[3.2.1]octane (follower). This product is identified by 2D NMR. Acetylation of cedarwood oil with 13C‐1 labeled acetic acid anhydride leads to a product labeled at the aromatic carbon C‐3′. From the 13C‐labeled compound 13C‐13C coupling constants could be measured. Acetyl cedrene is conveniently deuteriated by an acid‐catalysed exchange reaction using trifluoroacetic anhydride and D2O. The product is found to be deuteriated both at the acetyl group and at the methyl group at the double bond (carbon 6). The reaction condition during deuteriation of cedrol leads to the elimination of the hydroxyl group at C‐6 with the formation of α ‐cedrene deuteriated at H‐5 and the methyl group at C‐6. Deuteriation of the follower leads to deuterium exchange at the aromatic carbons C‐5′ and C‐6′. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
6.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(9):757-771
Results are reported on the regioselective C‐deuteriation of a series of silyl enol ethers derived from aryl alkyl ketones using deuterium (D2) gas as the deuterium source and palladium‐on‐barium sulfate as the mediator. These results highlight the numerous reaction pathways and different product types available from simple deuteriation of substituted enol precursors. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
7.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(11):1033-1053
Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the addition of sec‐BuLi to a variety of substituted amides. The outcomes of the reactions are discussed in terms of the structural nature of the amides and the deuteriated sources employed. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
8.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(11):985-996
The acetate salt of 2,5‐bis[5‐amidino‐2‐pyridyl]furan‐d2/15N2 ( 4) was synthesized from 2,5‐bis[5‐cyano‐2‐pyridyl]furan‐d2 ( 2 ), through the bis‐O‐acetoxyamidoxime followed by hydrogenation. Compound 2 was obtained via a Stille coupling reaction of 6‐chloronicotinonitrile with 2,5‐bis[tri‐n‐butyltin]‐furan‐d2 ( 1 ). 2,5‐bis[5‐amidino‐2‐pyridyl)furan‐d6 ( 10) was synthesized from 2,5‐bis[5‐cyano‐2‐pyridyl)furan‐d6 ( 9 ) via a direct reaction with lithium bis(trimethylsilyl)amide, followed by deprotection with ethanolic HCl. 15N and/or deuterium‐labelled methoxy‐amidines 5a ‐d2/15N2, 5b ‐d8, 12 , 14 ‐d6 were prepared in good yield via direct methylation of their respective diamidoximes with either dimethylsulfate‐d0 or dimethylsulfate‐d6 in DMF solution and using LiOH as a base. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
9.
Alexey V. Salin Rashid Z. Musin 《Journal of labelled compounds & radiopharmaceuticals》2018,61(8):595-598
2‐d‐Acrylamide was synthesized via the 2‐step procedure starting from acrylonitrile and deuterium oxide. This procedure affords 2‐d‐acrylamide in 99.9% chemical purity and 98.4% isotopic enrichment. 相似文献
10.
Colette May Carol Downey John D. Power Pierce V. Kavanagh 《Drug testing and analysis》2020,12(9):1387-1392
The identification of tert‐butyl‐4‐anilinopiperidine‐1‐carboxylate (4‐anilinopiperdine‐t‐BOC or 4‐AP‐t‐BOC) in many seized falsified ‘Xanax’ tablets has been reported after being encountered in forensic casework in late 2019 and early 2020 in Ireland. This substance was also detected in a pink powder submitted for analysis in March 2020. The pink powder was part of a larger seizure comprising brown powders which contained morphine or diamorphine (heroin) or a type of counterfeit heroin or heroin adulterant (known as ‘bash’). Novel benzodiazepines and other substances are being detected as ingredients in falsified benzodiazepine tablets more frequently on the illicit market. The detection of 4‐AP‐t‐BOC in benzodiazepine tablets is noteworthy and 4‐AP‐t‐BOC is added to the list of adulterants found in benzodiazepine tablets emerging in Europe. The presence of 4‐AP‐t‐BOC in both falsified ‘Xanax’ and powdered seizures is unusual, and analytical data are presented to assist with the identification of this compound in suspected illicit substances. The presence of 4‐AP‐t‐BOC in the tablets was confirmed using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analyses, and spectral fragmentation pathways were suggested. To the authors' best knowledge, information about the biological activity of 4‐AP‐t‐BOC is not available. The removal of the t‐BOC protecting group yields 4‐anilinopiperidine which has been reported to be involved in the synthesis of fentanyl. 相似文献
11.
Among various strategies, the de novo design and in silico approaches are being used to develop the short peptides, models of modified peptides, and mimetics as clinically useful drugs with improved stability and bioavailability. The resulting models will help to isolate the factors behind the folded structure formation and contribute useful information about de novo peptide design. The combined 1H‐NMR spectroscopic and molecular dynamics methods were used to investigate the conformational behavior of an Arg‐Gly‐Asp (RGD)‐containing peptide, GRGDSPC, the cell‐binding heptapeptide of extracellular matrix protein, fibronectin. The formation of two fused weak β‐turns of type II (HB, 4→1) and type II’ (HB, 7→4) from simulation studies has been consistent with NMR data. The sustainable ‘S’‐shaped molecular structure (which remained unchanged during the entire simulation) and the conformational transitions due to interconversions between multiple turns initiated at Asp4, Ser5, and Cys7 imply that the peptide is flexible in nature. Thus, the model of ‘S’‐shaped structure with flexible multiple turns for GRGDSPC peptide may provide the structural rationale for antagonistic properties of this heptapeptide toward the treatment of integrin‐mediated cellular abnormal behaviors such as thrombosis and metastasis. 相似文献
12.
Hong Zhao 《Journal of labelled compounds & radiopharmaceuticals》2008,51(7):293-296
The synthesis and crystal structures of deuterium‐labeled 5‐substituted 1H‐tetrazoles, 5‐[2H5]phenyl‐1H‐tetrazole (I), 5‐[2H7]tolyl‐1H‐tetrazole (II), and 5‐[2H7]benzyl‐1H‐tetrazole (III) are reported. All syntheses were carried out using simple, facile steps and the products were obtained in high yields. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
13.
Billie Bonevski 《Drug and alcohol review》2014,33(1):99-101
Patient‐centred tobacco management is a pragmatic approach for helping smokers achieve their goals in terms of either cessation or harm reduction. However, the success of the approach is dependent on clinicians embracing and delivering it as intended. There are a number of structural and systemic organisational barriers which are limiting clinician‐delivered patient‐centred tobacco dependence. In response, ‘whole system’ approaches which help support clinicians in the delivery of patient‐centred tobacco management are required. Health system changes to support clinicians and facilitate the delivery of patient‐centred tobacco management are worth further investigation, particularly in settings where tobacco smoking rates are high. [Bonevski B. System‐centred tobacco management: From ‘whole‐person’ to ‘whole‐system’ change. Drug Alcohol Rev 2014;33:99–101] 相似文献
14.
Abstract: A brief survey of the history of peptide chemistry from Theodore Curtius to Emil Fischer to Bruce Merrifield is first presented. The discovery and development of peptide ligation, i.e. of actual chemical synthesis of proteins are described. In the main chapter, ‘ Synthesis of Proteins by Chemical Ligation ’ a detailed discussion of the principles, reactivities and mechanisms involved in the various coupling strategies now applied (ligation, chemical ligation, native chemical ligation) is given. These include coupling sites with cysteine and methionine (as well as the seleno analogs), histidine, glycine and pseudo‐prolines, ‘unrestricted’ amino‐acid residues (using the Staudinger reaction), as well as solid‐phase segment coupling by thioligation of unprotected peptides. In another section, ‘ Synthesis of β‐peptides by Thioligation ’, couplings involving β2‐ and β3‐peptides are described (with experimental details). 相似文献
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16.
Abstract: Dermorphin and [Lys7]dermorphin, selective µ‐opioid receptor ligands originating from amphibian skin, have been modified with various electrophiles in either the ‘message’ or ‘address’ sequences as potential peptide‐based affinity labels for µ‐receptors. Introduction of the electrophilic isothiocyanate and bromoacetamide groups on the para position of Phe3 and Phe5 was accomplished by incorporating Fmoc‐Phe(p‐NHAlloc) into the peptide followed by selective deprotection and modification. The corresponding amine‐containing peptides were also prepared. The pure peptides were evaluated in radioligand binding experiments using Chinese hamster ovary (CHO) cells expressing µ‐ and δ‐opioid receptors. In dermorphin, introduction of the electrophilic groups in the ‘message’ domain lowered the binding affinity by > 1000‐fold; only [Phe(p‐NH2)3]dermorphin retained nanomolar affinity for µ‐receptors. Modifications in the ‘address’ region of both dermorphin and [Lys7]dermorphin were relatively well tolerated. In particular, [Phe(p‐NH2)5,Lys7]dermorphin showed similar affinity to dermorphin, with almost 2‐fold higher selectivity for µ‐receptors. [Phe(p‐NHCOCH2Br)5]‐ and [Phe(p‐NHCOCH2Br)5,Lys7]dermorphin exhibited relatively high affinity (IC50 = 27.7 and 15.1 nm , respectively) for µ‐receptors. However, neither of these peptides inhibited [3H]DAMGO binding in a wash‐resistant manner. 相似文献
17.
Synthesis of two potent glucocorticoid receptor agonists labeled with carbon‐14 and stable isotopes
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Bachir Latli Jonathan T. Reeves Zhulin Tan Matt Hrapchak Jinhua J. Song Carl B. Busacca Chris H. Senanayake 《Journal of labelled compounds & radiopharmaceuticals》2015,58(11-12):445-452
Two potent glucocorticoid receptor agonists were prepared labeled with carbon‐14 and with stable isotopes to perform drug metabolism, pharmacokinetics, and bioanalytical studies. Carbon‐14 labeled (1) was obtained from an enantiopure alkyne (5) via a Sonogashira coupling to a previously reported 5‐amino‐4‐iodo‐[2‐14C]pyrimidine [14C]‐(6), followed by a base‐mediated cyclization (1) in 72% overall radiochemical yield. Carbon‐14 labeled (2) was prepared in five steps employing a key benzoic acid intermediate [14C]‐(13), which was synthesized in one pot from enolization of trifluoromethylketone (12), followed by bromine–magnesium exchange and then electrophile trapping reaction with [14C]‐carbon dioxide. A chiral auxiliary (S)‐1‐(4‐methoxyphenyl)ethylamine was then coupled to this acid to give [14C]‐(15). Propargylation and separation of diastereoisomers by crystallizations gave the desired diastereomer [14C]‐(17) in 34% yield. Sonogashira coupling to iodopyridine (10) followed by cyclization to the azaindole [14C]‐(18) and finally removal of the chiral auxiliary gave [14C]‐(2) in 7% overall yield. For stable isotope syntheses, [13C6]‐(1) was obtained in three steps using [13C4]‐(6) and trimethylsilylacetylene‐[13C2] in 26% yield, while [2H5]‐(2) was obtained by first preparing the iodopyridine [2H5]‐(10) in five steps. Then, Sonogashira coupling to chiral alkyne (24) and cyclization gave [2H5]‐(2) in 42% overall yield. 相似文献
18.
Chao Li Xiao‐Yong Xu Xuan‐Qi Liu Qiu‐Guo Fu Wei Wang Qing‐Fu Ye Zhong Li 《Journal of labelled compounds & radiopharmaceuticals》2012,55(9):339-345
To support the metabolism and toxicology study of cis‐neonicotinoids, radio or stable isotope was introduced into different sites of the key intermediate 2‐chloro‐5‐((2‐(nitromethylene)imidazolidin‐1‐yl)methyl)pyridine (6‐Cl‐PMNI). [3H2]‐ and [14C]‐label were successively prepared from initial materials NaB3H4 and [14C]‐nitromethane, respectively. Similarly, [D2]‐6‐Cl‐PMNI was prepared from NaBD4 in four steps, with 52.6% overall isotopic yield, and dual‐labeled [D2, 13C]‐target was obtained from NaBD4 and [13C]‐nitromethane, affording overall isotopic yield of 42.5%. Moreover, [14C2] was introduced from [U‐14C]‐ethylenediamine dihydrochloride in three steps, with a 58.3% overall chemical yield. Finally, typical labeled cis‐neonicotinoids paichongding and cycloxaprid were prepared and characterized. The methods were proved to have good generality in the synthesis of other cis‐neonicotinoids, and all results would be useful in metabolism studies of new cis‐neonicotinoids. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
19.
Stuart J. Rozze M. Jonathan Fray 《Journal of labelled compounds & radiopharmaceuticals》2009,52(10):435-442
The preparation of deuterated PF‐2413873 (4‐[3‐cyclopropyl‐1‐(methanesulfonylmethyl)‐5‐methyl‐1H‐pyrazol‐4‐yl]oxy‐2,6‐dimethylbenzonitrile, 1) is described for use as a bioanalytical standard in clinical trials. Two strategies were investigated. The sulfone‐containing substituent was labelled by base‐catalyzed exchange, but unacceptable deuterium loss was noted under assay conditions. Alternatively, labelling 4‐cyano‐3,5‐dimethylphenol was achieved by heating with deuterium oxide over platinum oxide. After building up the pyrazole ring we discovered that, during the subsequent alkylation to attach the methylthiomethyl group, the base, potassium t‐butoxide, caused unwanted scrambling of deuteriums on the aromatic portion and the methylthiomethyl group. Thus, it was necessary to remove all base‐labile hydrogens to prevent their exchange. This was accomplished by alkylating the pyrazole with per‐deuterated chloromethyl methylsulfide, oxidation to the sulfone, and selective removal of its deuteriums by treatment with sodium hydroxide. The unusual sensitivity and selectivity of these base‐promoted exchange reactions are discussed. Thus, 4‐[3‐cyclopropyl‐1‐(methanesulfonylmethyl)‐5‐methyl‐1H‐pyrazol‐4‐yl]oxy‐[2H6]2,6‐dimethyl‐[3,5‐2H]benzonitrile (17) was obtained, labelled with eight deuterium atoms and an acceptable D0/D8 ratio. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
20.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(4):233-242
6‐[5‐(4‐Amidinophenyl)furan‐2‐yl]nicotinamidine‐d4 ( 5 ) was synthesized from 6‐[5‐(4‐cyanophenyl)furan‐2‐yl]nicotinonitrile‐d4 ( 3 ), through the bis‐O‐acetoxy‐amidoxime followed by hydrogenation. Compound 3 was prepared from 6‐(furan‐2‐yl)‐nicotinonitrile by a Heck coupling reaction with 4‐bromobenzonitrile‐d4, a product of selective cyanation reaction of 1,4‐dibromobenzene‐d4 with Cu(1)CN. Deuterium‐labelled N‐methoxy‐6‐{5‐[4‐(N‐methoxy‐amidinophenyl]‐furan‐2‐yl}‐nicotinamidines were prepared via methylation of their respective amidoximes with dimethyl sulfate‐d6 in aqueous sodium hydroxide in good yields. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献