108549-23-1Relevant academic research and scientific papers
Synthesis of Phospho-Polypeptides via Phosphate-Containing N-Carboxyanhydride: Application in Enzyme-Induced Self-Assembly, and Calcium Carbonate Mineralization
Das, Soumen,Dutta, Tahiti,Gupta, Sayam Sen,Mondal, Basudeb,Panda, Sidharth
, p. 1053 - 1064 (2020)
An easy synthetic strategy was developed to synthesize the phosphate-functionalized amino acid N-carboxyanhydride (NCA), using simple primary amine initiators to obtain homo and block phospho-polypeptides with controlled molecular weight and molecular weight distribution. The methodology was extended to the synthesis of the end-functionalized homo polypeptides (15 to 50 repeat unit) and block co-polypeptides with PEG (0.7 K, 2 K, and 5 K) and glycopolypeptide (15-unit mannose glycopolypeptide) as one of the blocks. The deprotected fully water-soluble anionic phosphate-based polypeptides showed pH-dependent helical conformation with a helical content of 20 %, which further changed to β-sheets upon addition of the enzyme alkaline phosphatase (ALP) due to dephosphorylation. The block co-polypeptide containing PEG as one of the blocks led to its self-assembly into colloidal structures, such as vesicles with a hydrodynamic diameter of ～250 nm, due to the formation of amphiphilic block co-polymer upon dephosphorylation. The nature of the colloidal structures formed can be temporally controlled by the extent of dephosphorylation. Finally, the phospho-polypeptides serve as a template for the mineralization of calcium carbonate with varying polymorphs and morphologies.
Phosphoric acid phaseomannite class compound and its preparation method and application (by machine translation)
-
Paragraph 0196; 0197, (2017/07/14)
The invention discloses a phaseomannite class phosphate compound, phosphoric acid phaseomannite class compound preparation method, and these phosphoric acid phaseomannite class compounds in the preparation of an anti-tumor drug. The use of non-small cell lung cancer cells to the compounds of this invention to inhibit the growth of tumor cells in active testing, that the compounds of this invention have high inhibition of tumor cell growth activity, some of the compound inhibiting activity even with cisplatin active quite, which indicates that the compounds of this invention have good cell penetrability and phosphorus esterase stability, can be used for the development of anti-tumor medicament. (by machine translation)
Synthesis of alkylcarbonate analogs of O-acetyl-ADP-ribose
Dvorakova, Marcela,Nencka, Radim,Dejmek, Milan,Zbornikova, Eva,Brezinova, Anna,Pribylova, Marie,Pohl, Radek,Migaud, Marie E.,Vanek, Tomas
, p. 5702 - 5713 (2013/09/12)
The non-hydrolyzable alkylcarbonate analogs of O-acetyl-ADP-ribose have been synthesized from the phosphorylated ribose derivatives after coupling with AMP morpholidate promoted by mechanical grinding. The analogs were assessed for their ability to inhibi
Optimized synthesis of phosphatidylserine
Guanti, Giuseppe,Banfi,Basso,Bondanza,Guglieri,Powles,Riva
experimental part, p. 367 - 373 (2010/12/18)
The synthesis of phosphatidyl serine containing saturated fatty acids was thoroughly studied and optimized in order to establish a protocol amenable to large-scale synthesis. The key step was a one-pot multicomponent reaction involving an O-benzyl phosphorodiamidite, protected serine and diacylglycerol, followed by in situ oxidation of the resulting phosphite. In order to replace expensive and poorly stable tetrazole, a screening of substitutes was carried out and imidazolium chloride was selected as the best suited one. Springer-Verlag 2010.
Synthesis of D- and L-myo-inositol 2,4,5-trisphosphate and trisphosphorothioate: structural analogues of D-myo-inositol 1,4,5-trisphosphate.
Mills, Stephen J,Liu, Changsheng,Potter, Barry V L
, p. 1795 - 1801 (2007/10/03)
The preparation of D- and L-myo-inositol 2,4,5-trisphosphate is described, together with the phosphorothioate counterparts. The known chiral diols D- and L-1,4-di-O-benzyl-5,6-bis-O-p-methoxybenzyl-myo-inositol were regioselectively protected at the 3-position using a benzyl group via a 2,3-O-stannylene acetal. Removal of the p-methoxybenzyl groups of each enantiomer gave D- and L-1,3,6-tri-O-benzyl-myo-inositol. Phosphitylation with bis(benzyloxy)diisoproplyaminophosphine and 1H-tetrazole gave the trisphosphite intermediate for each enantiomer. Oxidation with 3-chloroperoxybenzoic acid gave the fully protected D- and L-myo-inositol 2,4,5-trisphosphates. Sulphoxidation of the D- and L-2,4,5-trisphosphite intermediates gave the fully protected D- and L-myo-inositol 2,4,5-trisphosphorothioate compounds. The fully protected trisphosphates were deblocked using hydrogenolysis and the phosphorothioates were deprotected using sodium in liquid ammonia. The individual compounds were then purified using ion exchange chromatography to afford pure D- and L-myo-inositol 2,4,5-trisphosphates together with the corresponding phosphorothioates.
Stereoselective synthesis of inositol mono, bis and trisphosphate analogue from 6-deoxy-D-inositol precursors
Vieira de Almeida, Mauro,Dubreuil, Didier,Cleophax, Jeannine,Verre-Sebrie, Catherine,Pipelier, Muriel,Prestat, Guillaume,Vass, Georges,Gero, Stephane D.
, p. 7251 - 7270 (2007/10/03)
The synthesis of opticaly pure deoxy-myo-inositol mono, bis and trisphosphate analogues is described from 4-O-benzyl-2,3-di-O- cyclohexylidene-6-deoxy-myo-inositol and corresponding 1,5 epimer chiro- inositol. These precursors, which derive from galactose, are used to accede to a variety of cyclitol intermediates employing protection/deprotection sequence. The phosphorylation procedure was performed to produce free and original substituted phosphate derivatives aimed to be incorporated through the lipidic cell membrane for in vivo evaluation.
Chiral cyclopentane-based mimics of D-myo-inositol 1,4,5-trisphosphate from D-glucose
Jenkins, David J.,Riley, Andrew M.,Potter, Barry V. L.
, p. 7719 - 7726 (2007/10/03)
Two routes from D-glucose to chiral, ring-contracted analogs of the second messenger D-myo-inositol 1,4,5-trisphosphate are described. Methyl α-D-glucopyranoside was converted by an improved procedure into methyl 4,6-O-(p-methoxybenzylidene)-α-D-glucopyranoside (6) and thence into methyl 2-O-benzyl-3,4-bis-O-(p-methoxybenzyl)-α-D-gluco-hexodialdopyranoside (1,5) (14) in four steps. In the first ring-contraction method 14 was converted into methyl 2-O-benzyl-6,7-dideoxy-3,4-bis-O-(p-methoxybenzyl)-α-D-gluco-hept-6-e nopyranoside (1,5) (15), which on sequential treatment with Cp2Zr(n-Bu)2 followed by BF3·Et2O afforded a mixture of (1R,2S,3S,4R,5S)-3-(benzyloxy)-4-hydroxy-1,2-bis[(p-methoxybenzyl)oxy] -5-vinylcyclopentane (16) and its 4S,5R diastereoisomer 17. Removal of the p-methoxybenzyl groups of 16 and subsequent phosphorylation and deprotection afforded the first target compound, (1R,2R,3S,4R,5S)-3-hydroxy-1,2,4-tris(phosphonooxy)-5-vinylcyclopentan e (3). In the second route, intermediate 14 was subjected to SmI2-mediated ring contraction to give (1R,2S,3S,4R,5S)-3-(benzyloxy)-4-hydroxy-5-(hydroxymethyl)-1,2-bis[(p- methoxybenzyl)oxy]cyclopentane (20). Benzylation of 20 provided (1R,2S,3S,4R,5S)-3-(benzyloxy)-6-[(benzyloxy)methyl]-4-hydroxy-1,2-bis [(p-methoxybenzyl)oxy]cyclopentane (22) and (1R,2S,3S,4R,5S)-3,4-bis(benzyloxy)-5-(hydroxymethyl)-1,2-bis[(p-metho xybenzyl)oxy]cyclopentane (21), which were elaborated to the target trisphosphates (1R,2R,3S,4R,5S)-3-hydroxy-5-(hydroxymethyl)-1,2,4-tris(phosphonooxy)c yclopentane (4) and (1R,2S,3R,4R,5S)-1,2-dihydroxy-3,4-bis(phosphonooxy)-5-[(phosphonooxy) methyl]cyclopentane (5), respectively. Both 3 and 4 mobilized intracellular Ca2+, but 4 was only a few fold less potent than D-myo-inositol 1,4,5-trisphosphate, demonstrating that effective mimics can be designed that do not bear a six-membered ring.
Synthesis of L-scyllo-inositol 1,2,4-trisphosphate, scyllo-inositol 1,2,4,5-tetrakisphosphate and phosphorothioate and DL-2-deoxy-2-fluoro-myo-inositol 1,4,5-trisphosphate: Optical resolution of DL-1-O-allyl-3,6-di-O-benzyl-4,5-O-isopropylidene-scyllo-inositol
Lampe, Dethard,Liu, Changsheng,Mahon, Mary F.,Potter, Barry V. L.
, p. 1717 - 1727 (2007/10/03)
Routes for the synthesis of scyllo-inositol tris- and tetrakis-phosphates and 2-deoxy-2-fluoro-myo-inositol 1,4,5-trisphosphate from myo-inositol have been devised. For DL-scyllo-inositol 1,2,4-trisphosphate, DL-1-O-allyl-3,6-di-O-benzyl-4-5-O-isopropylidene-scyllo-inositol was prepared from the triflate of DL-1-O-allyl-3,6-di-O-benzyl-4,5-O-isopropylidene-myo-inositol by inversion at C-2. Removal of the isopropylidene group and phosphorylation gave the protected trisphosphate. Deblocking with sodium in liquid ammonia afforded racemic scyllo-inositol 1,2,4-trisphosphate. DL-1-O-Allyl-3,6-di-O-benzyl-4,5-O-isopropylidene-scyllo-inositol was resolved into its enantiomers by means of the crystalline 2-O-camphanate ester. The structure of one diastereoisomer, 1D-O-allyl-3,6-di-O-benzyl-2-O-[( - )-camphanoyl]-4,5-O-isopropylidene-scyllo-inositol was determined by single-crystal X-ray crystallography. 1D-( + )-1-O-Allyl-3,6-di-O-benzyl-4,5-O-isopropylidene-scyllo-inositol was used to prepare 1L-( - )-scyllo-inositol 1,2,4-trisphosphate in a fashion analogous to the racemic modification. DL-1-O-Allyl-3,6-di-O-benzyl-scyllo-inositol was isomerised to the (Z)-prop-1-enyl derivative. The propenyl group was then removed to give the meso-1,4-di-O-benzyl-scyllo-inositol. Phosphitylation followed by oxidation or sulfoxidation gave the fully protected tetrakis-phosphate or -phosphorothioate, respectively. After deblocking and purification, scyllo-inositol 1,2,4,5-tetrakisphosphate and scyllo-inositol 1,2,4,5-tetrakisphosphorothioate were obtained. DL-1-O-Allyl-3,6-di-O-benzyl-4,5-O-isopropylidene-scyllo-inositol was isomerised to the 1-O-[(Z)-prop-1-enyl] derivative which was converted into the 2-0-triflate. Displacement of the triflate using tetrabutylammonium fluoride proceeded with inversion of configuration to give DL-3,6-di-O-benzyl-2-deoxy-2-fluoro-4,5-O-isopropylidene-1-O-([(Z)-prop-1-enyl]- myo-inositol. Removal of propenyl and isopropylidene groups afforded DL-3,6-di-O-benzyl-2-deoxy-2-fluoro-myo-inositol, which was phosphitylated and the product oxidised to give the fully protected 2-fluoro trisphosphate. Deprotection furnished DL-2-deoxy-2-fluoro-myo-inositol 1,4,5-trisphosphate. These compounds will be useful probes for investigation of the polyphosphoinositide pathway of cellular signalling.
Unambiguous Total Synthesis of the Enantiomers of myo-Inositol 1,3,4-Trisphosphate: 1L-myo-Inositol 1,3,4-Trisphosphate Mobilizes Intracellular Ca2+ in Limulus Photoreceptors
Riley, Andrew M.,Payne, Richard,Potter, Barry V. L.
, p. 3918 - 3927 (2007/10/02)
Syntheses of the enantiomers of myo-inositol 1,3,4-trisphosphate are described. 1,4-Di-O-allyl-myo-inositol was regioselectively p-methoxybenzylated at the 3-position to give 1,4-di-O-allyl-3-O-(p-methoxybenzyl)-myo-inositol followed by benzylation of the remaining free hydroxyl groups to give the key intermediate 1,4-di-O-allyl-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol.Removal of the p-methoxybenzyl and allyl groups gave 2,4,5-tri-O-benzyl-myo-inositol which was-phosphitylated with bis(benzyloxy)(diisopropylamino)phosphine to give the fully protected trisphosphite triester.Oxidation using tert-butyl hydroperoxide gave 2,5,6-tri-O-benzyl-1,3,4-tris(dibenzylphospho)-myo-inositol, and deprotection using sodium in liquid ammonia gave racemic myo-inositol 1,3,4-trisphosphate.Deprotection of the key intermediate 1,4-di-O-allyl-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol by isomerization of allyl groups followed by mild acid hydrolysis gave 2,4,5-tri-O-benzyl-1-O-(p-methoxybenzyl)-myo-inositol, which was converted to the diastereoisomeric bis-(-)-camphanates.The diastereoisomers were separated by column chromatography and the camphanates and the p-methoxybenzyl group removed by saponification and acid hydrolysis, respectively, for each diastereoisomer to give the enantiomers of 2,4,5-tri-O-benzyl-myo-inositol.The absolute configurations of the latter were established by conversion of 1L-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol to the known 1L-1,2,4,5,6-penta-O-benzyl-myo-inositol.Phosphorylation and deblocking gave the D- and L-enantiomers of myo-inositol 1,3,4-trisphosphate.Biological evaluation in Limulus photoreceptors showed that 1L-myo-inositol 1,3,4-trisphosphate was much more active than the D-enantiomer, producing repetitive bursts of depolarization due to mobilization of intra cellular calcium.
Synthesis, Bioactivity and Anti-HIV Activity of the Bis(4-acyloxybenzyl) and Mono(4-acylaoxybenzyl) Esters of the 5'-Monophosphate of AZT
Thomson, William,Nicholls, Dave,Irwin, William J.,Al-Mushadani, Julian S.,Freeman, Sally,et al.
, p. 1239 - 1246 (2007/10/02)
To investigate the design of prodrugs of antiviral nucleosides for targeting to the central nervous system, the bis(4-acyloxybenzyl) esters of the 5'-monophosphate of AZT 5 (R = Me, Et, Pri or But) have been prepared.The reaction of the appropriate bis(4-acyloxybenzyl) N,N-diisopropylphosphoramidite 10 (R = Me, Et, Pri or But) with AZT in the presence of 1H-tetrazole, followed by oxidation of the PIII intermediate with 3-chloroperoxybenzoic acid gave the required triesters 5 in good yield.The lithium salts of the mono(4-acycloxybenzyl) esters of the 5'-phosphate of AZT 7 (R = Me, Et, Pri or But) were prepared by treatment of the triesters 5 with lithium iodide.In the presence of porcine liver carboxyesterase the triesters 5 and diesters 7 decomposed readily to the 5'-monophosphate of AZT 9.The anti-HIV activities of the triesters 5 and diesters 7 were, with one exception, comparable to that of AZT, but the greater cytotoxicity of certain compounds in particular types of cell significantly reduced their selectivity indices.
