An optimized and scalable synthesis of propylphosphonic anhydride for general use

Pizova, Hana; Bobáľ, Pavel

doi:10.1016/j.tetlet.2015.02.126

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…Photoinduced free‐radical hydrophosphonylation of 7 a–e , following the protocol developed by Dondoni and co‐workers, afforded phosphonates 8 a – e with complete regioselectivity and good yields (Scheme ). Removal of the protecting groups of 8 d under typical conditions led to free phosphonate 9 d in excellent yield. Any attempt to couple compound 9 d with 10 in the presence of N , N ′‐dicyclohexylcarbodiimide (DCC) failed, as well as deprotection of both OMe groups.…”

Section: Resultsmentioning

confidence: 99%

Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less‐Polar Conjugates

Ghirardello

Rivas

Lacetera

et al. 2016

Chemistry A European J

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The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.

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Section: Resultsmentioning

confidence: 99%

Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less‐Polar Conjugates

Ghirardello

Rivas

Lacetera

et al. 2016

Chemistry A European J

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“…In the original procedure for the synthesis of compound 25, POCl 3 in pyridine was used. Only amide 25 was prepared to satisfactory yield since the attempts to apply this method for the synthesis of other amide derivatives were unsuccessful [49,50]. The major problem in these syntheses seems to be desilylation and subsequent uncontrolled coupling reactions.…”

Section: Resultsmentioning

confidence: 99%

SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors

Bąk

Pizova

Kozik

et al. 2019

IJMS

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A set of 25 novel, silicon-based carbamate derivatives as potential acetyl- and butyrylcholinesterase (AChE/BChE) inhibitors was synthesized and characterized by their in vitro inhibition profiles and the selectivity indexes (SIs). The prepared compounds were also tested for their inhibition potential on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. In fact, some of the newly prepared molecules revealed comparable or even better inhibitory activities compared to the marketed drugs (rivastigmine or galanthamine) and commercially applied pesticide Diuron®, respectively. Generally, most compounds exhibited better inhibition potency towards AChE; however, a wider activity span was observed for BChE. Notably, benzyl N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(2-hydroxyphenyl)carbamoyl]ethyl]-carbamate (2) and benzyl N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(3-hydroxyphenyl)carbamoyl]ethyl]-carbamate (3) were characterized by fairly high selective indexes. Specifically, compound 2 was prescribed with the lowest IC50 value that corresponds quite well with galanthamine inhibition activity, while the inhibitory profiles of molecules 3 and benzyl-N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(4-hydroxyphenyl)carbamoyl]ethyl]carbamate (4) are in line with rivastigmine activity. Moreover, a structure–activity relationship (SAR)-driven similarity evaluation of the physicochemical properties for the carbamates examined appeared to have foreseen the activity cliffs using a similarity–activity landscape index for BChE inhibitory response values. The ‘indirect’ ligand-based and ‘direct’ protein-mediated in silico approaches were applied to specify electronic/steric/lipophilic factors that are potentially valid for quantitative (Q)SAR modeling of the carbamate analogues. The stochastic model validation was used to generate an ‘average’ 3D-QSAR pharmacophore pattern. Finally, the target-oriented molecular docking was employed to (re)arrange the spatial distribution of the ligand property space for BChE and photosystem II (PSII).

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“…From conventional and emerging chemical approaches for amide bond formation [ 3 , 36 , 37 , 38 , 39 , 40 ] and from the methods which have been previously used in our laboratories [ 8 , 41 , 42 , 43 ], we have selected the procedure where propylphosphonic anhydride (T3P) has been used as a coupling agent [ 43 ]. The application of this one-pot reaction to commercially available (2 S )-1-[(benzyloxy)carbonyl]-pyrrolidine-2-carboxylic acid and a wide variety of substituted anilines led to the formation of corresponding substituted anilides 1 – 8c (see Scheme 1 ) that were isolated in high yields and high purity.…”

Section: Resultsmentioning

confidence: 99%

Proline-Based Carbamates as Cholinesterase Inhibitors

et al. 2017

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Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC50 = 46.35 μM) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC50 = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure–inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3′-/4′-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE.

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An optimized and scalable synthesis of propylphosphonic anhydride for general use

Cited by 15 publications

References 24 publications

Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less‐Polar Conjugates

Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less‐Polar Conjugates

SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors

Proline-Based Carbamates as Cholinesterase Inhibitors

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