- A three-acetyl deoxyribose α isomer preparation method
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The invention discloses a capecitabine intermediate impurity tri acetyl deoxyribose α isomer: the chemical name is 1 α - 1, 2, 3 - three-acetoxy - 5 - deoxy - D - ribose of the preparation method. The preparation method in order to 5 - deoxy - D - ribose as a synthetic raw material, by isopropenyl acetate/iron trichloride acetylation than three acetyl deoxyribose α isomer crude, passes through the column again chromatography purification to obtain the triacetyl deoxyribose α isomer pure product. The invention provides a triacetyl deoxyribose α isomer preparation method, with simple operation, the advantage of the high product purity, for capecitabine intermediate and the quality of the finished good foundation for the study.
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- AMPHIPHILE PRODRUGS
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Amphiphilic prodrugs of general formula A-X are disclosed, wherein A is a biologically active agent or may be metabolised to a biologically active agent; and X is selected from the group consisting of R, or up to three R moieties attached to a linker, Y1, Y2 or Y3, wherein R is selected from a group consisting of alkyl, alkenyl, alkynyl, branched alkyl, branched alkenyl, branched alkynyl, substituted alkyl, substituted alkenyl and substituted alkynyl groups and their analogues; Y1 is a linker group which covalently attached to an R group at one site and is attached to A at a further independent site; Y2 is a linker group which is covalently attached to two R groups at two independent sites and is attached to A at a further independent site; and Y3 is a linker group which is covalently attached to three R groups at three independent sites and is attached to A at a further independent site. Self-assembly of the amphiphilic prodrugs into reverse lyotropic phases, particularly hexagonal, cubic and sponge, is disclosed. In preferred embodiments A is dopamine or a 5-fluorouracil prodrug.
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Paragraph 0142; 0149; 0150
(2019/06/12)
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- 3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation
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Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5′-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. 2-Nitrophenylhydrazonopyra-zolone derivative 5 showed significant activity against MERS-CoV (EC50 = 4.6 μM). The nucleoside analog 8 showed moderate activity against DENV-2 (EC50 = 10 μM), while the activity was abolished with the corresponding 5′-deoxyribonucleoside analogs. The identified hits in this study set this category of compounds for further future optimizations.
- Ahmed, Ayman M. S.,Abou-Elkhair, Reham A. I.,El-Torky, Alaa M.,Hassan, Abdalla E. A.
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p. 590 - 603
(2019/04/03)
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- Preparation method of capecitabine intermediate
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The invention discloses a preparation method of a capecitabine intermediate 1, 2, 3-O-triacetyl-5-deoxy-D-furanoside, which belongs to the technical field of medicinal chemistry. According to the invention, D-ribose (a compound I) is used as an initial raw material, and is subjected to a protective group reaction with methanol and acetone under the catalysis of solid acid, 1, 2, 3-hydroxyl is protected to obtain a compound II, then the compound II and thionyl chloride are subjected to a chlorination reaction, hydroxymethyl is changed into chloromethyl, a compound III is obtained, the compoundIII is subjected to a reduction reaction through platinum/carbon catalytic hydrogenation to obtain a compound IV, the compound IV is subjected to acidic hydrolysis to obtain a compound V, and the compound V is subjected to acetylation to obtain a target compound VI. The whole process is short in reaction step and high in economy; side reactions are few, and product purity is high; no wastewater isgenerated in the first three steps, so that the method is more environment-friendly; and the method is beneficial to industrial production of the capecitabine intermediate 1, 2, 3-O-triacetyl-5-deoxy-D-furanoside.
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- Preparation method of high-purity capecitabine key intermediate
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The invention discloses a preparation method of a high-purity capecitabine key intermediate. The preparation method comprises the following steps: taking D-ribose as an initial raw material, performing hydroxyl protection, 5-site tosylation, reduction, deprotection and acetylation to obtain high-purity 1,2,3-O-triacetyl-5-deoxo-D-ribose, wherein the 5-site tosylation reaction is carried out in anorganic solvent 1 by adopting inorganic base 1. Meanwhile, the acetylation reaction is carried in the presence of alkali 2 by taking water as a reaction solvent and taking 4-dimethylamiopryidine as acatalyst. The preparation method disclosed by the invention is mild in reaction conditions, high in yield, economic and effective, the purity of the prepared 1,2,3-O-triacetyl-5-deoxo-D-ribose can reach 99.0%, the alpha-isomer is small in content even is not detected, and the preparation method is applicable to large-scale industrial production.
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Paragraph 0055; 0056; 0057
(2019/03/06)
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- Preparation method of 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribose
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The invention discloses a preparation method of 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribose, which belongs to the field of nucleoside medicine synthesis. The reaction steps of the preparation method areas follows: inosine reacts as a raw material with organic boronic acid to protect 2' and 3' hydroxyl groups, room-temperature reduction is then carried out under the condition of potassium borohydrideand trifluoroacetic acid, diol exchange deprotection is then carried out, and finally, acetic anhydride is added for reflux reaction, so that the 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribose is obtained.The synthesis method has the advantages of easy obtainment of the raw material, short steps and high process safety, and has an industrial application prospect.
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Paragraph 0023-0029; 0030-0036; 0037-0043; 0044-0057
(2018/07/30)
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- Method for preparing 1,2,3-tris-O-acetyl-5-deoxy-beta-D-ribose
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The invention discloses a method for preparing 1,2,3-tris-O-acetyl-5-deoxy-beta-D-ribose and belongs to the field of nucleoside synthesis in organic chemistry. The method comprises the following reaction steps: reacting inosine and halogenated sulfoxide to obtain a compound 2; reducing the compound 2 at lithium metal, and adding ammonium hydroxide for deprotection so as to obtain a compound 3; reacting the compound 3 in acetic anhydride under catalysis of inorganic boric acid, thereby obtaining the 1,2,3-tris-O-acetyl-5-deoxy-beta-D-ribose. The synthetic method is cheap in raw materials, shortin steps and easy for industrial production and has industrial application prospects.
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Paragraph 0030; 0031; 0036; 0037; 0043; 0050; 0057
(2018/09/21)
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- Preparation method of 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribose
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The invention discloses a preparation method of 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribose, and belongs to the field of nucleoside synthesis in organic chemistry. The method comprises reaction steps asfollows: inosine 1 and triphenyl phosphite-halogen are subjected to a reaction, and a compound 2 is obtained; then the compound 2 is subjected to hydrogenation reduction under palladium/carbon catalysis; an obtained compound 3 is subjected to a reaction in acetic anhydride under catalysis of inorganic boric acid, and 1,2,3-tri-O-acetyl-5-deoxy-beta-D-ribose is obtained. The synthesis method adoptscheap raw materials and short steps and has industrial application prospect, and industrial production is easy.
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Page/Page column 5-7
(2018/11/22)
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- Synthetic method of 1,2,3-tri-O-acetyl-5-deoxy-D ribose
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The invention provides a synthetic method of 1,2,3-tri-O-acetyl-5-deoxy-D ribose. The synthetic method comprises the steps of with D ribose as a starting raw material, protecting a site 1 of D ribose by virtue of isopropyl, protecting sites 2 and 3 by virtue of propylidene, removing 5-site hydroxyl through reduction, carrying out deprotection on the sites 2 and 3, and carrying out acetylation, so as to obtain a target product. The total yield of the route is 64% and is greatly superior to that of a traditional process, and particularly, the final product is a pure beta isomer and is easily recrystallized, purified and produced in a large scale.
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- Capecitabine and wherein the intermediate preparation method
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The invention discloses a preparation method of capecitabine. The method comprises the following steps: based on D-ribose serving as a starting raw material, carrying out hydroxyl protection, 5-site tosylation, iodine substitution, hypophosphorous acid deiodination and acetylation so as to obtain the key intermediate 12,3-tri-O-acetyl-5-deoxy-beta-D-ribofuranose; carrying out glycosylation on the key intermediate and 5-fluorocytosine; and finally, carrying out N-4 site acylation and deprotection so as to obtain the capecitabine. In the method, a metal catalyst dose not need to be used for participating in reaction, the reaction condition is mild, and the yield is high, thus the method is economical and effective as well as suitable for industrial production on a large scale.
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- Safe and Alternate Process for the Reductions of Methanesulfonates: Application in the Synthesis of 1,2,3-Triacetyl-5-deoxy-d-ribofuranoside
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Diethylene glycol dimethyl ether, diglyme, and 1,2-bis(2-methoxyethoxy)ethane, triglyme, are found to be suitable and safe alternate solvents to DMSO for the reduction of methanesulfonate in sodium borohydride. Addition of anhydrous lithium chloride led to the complete reduction of methanesulfonate esters to the corresponding alkanes in the presence of sodium borohydride in these solvents (diglyme and triglyme). This protocol is useful in the preparation of 1,2,3-triacetyl-5-deoxy-d-ribofuranoside, 7, a key intermediate of Capecitabine, 1, on the commercial scale.
- Mekala, Nagaraju,Moturu, Murthy V.R.K.,Dammalapati, Rao V.L.N.,Parimi, Atchuta R.
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p. 609 - 614
(2016/04/04)
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- PROCESS FOR PRODUCTION OF RIBOFURANOSE DERIVATIVES
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It is an object of the present Invention to provide a process for producing 1,2,3-tri-O-acetyl-5-deoxy-ribofuranose in an industrially appropriate manner. The present invention provides a process for producing a 1,2,3-tri-O-acetyl-5-deoxy-ribofuranose which comprises hydrogenating a compound represented by the formula (1) or formula (2) in the presence of a metal catalyst: wherein P1 and P2 independently represent a hydrogen atom or an acyl group OP1 and OP2 may together form an acetal group, and R represents a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, or an acyl group; wherein X1 represents Br or I, P3 and P4 independently represent a hydrogen atom or an acryl group, and R represents a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, or an acyl group.
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Page/Page column 23
(2010/08/07)
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- NOVEL PROCESS FOR THE RECOVERY OF BETA ACETYLFURANOSIDE
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There is provided an improved method for the recovery of residual, unseparated β-ACF from reaction mixtures remaining from an initial synthesis of ACF, which is in particular usable on a large industrial scale, more particularly in the production of capecitabine.
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Page/Page column 3
(2010/08/07)
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- METHOD FOR THE PREPARATION OF CAPECITABINE AND INTERMEDIATES USED IN SAID METHOD
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A process to obtain capecitabine compound and its pharmaceutically acceptable derivatives is hereby disclosed. Likewise, novel intermediates to be used in the preparation of capecitabine compound and its pharmaceutically acceptable derivatives are also disclosed. The procedure comprises the stage of causing a reaction of N4-(n-pentyloxycarbonyl))-5- fluorocytosine with (1,2,3-tri-O-acetyl-5-deoxy- α,β-D-ribofuranose.
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Page/Page column 8-9
(2010/11/03)
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- METHOD FOR STEREOSELECTIVE PREPARATION AND SEPARATION OF TRI-O-ACETYL-5-DEOXY-β-D-RIBOFURANOSE
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The present invention discloses a method for preparing highly pure tri-O-acetyl-5-deoxy-β-D-ribofuranose which comprises a highly stereoselective acetylation step of 1-methylacetonide, and the pure β-anomer thus obtained can be advantageous used for preparing capecitabine.
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Page/Page column 11-12
(2008/12/07)
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- PYRAZOLO[3, 4-D]PYRIMIDINE DERIVATIVES AS ANTIBACTERIAL COMPOUNDS
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This invention relates to 6-oxy-4-amino-1-(tetrahydrofuranyl)-1H- pyrazolo[3,4-d]pyrimidin-3(2H)-ones in free or salt form, e.g., compounds of formula (I) and formula (II) their use, e.g., in the treatment of bacterial infections and the process of preparing said compounds.
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Page/Page column 33-34
(2008/12/04)
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- Synthesis of 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose from D-ribose
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A practical route towards the synthesis of 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose from D-ribose is described. The key steps include deoxygenation of methyl 2,3-O-isopropylidene-5-O-sulfonyloxy-β-D-ribofuranoside by reductive displacement employing hydride reagents. Subsequent total hydrolysis followed by acetylation led to the title compound in 56% overall yield from D-ribose. The sequence is simple, inexpensive, high yielding and clearly suitable for multi-gram preparations.
- Sairam, Pothukuchi,Puranik, Ramachandra,Sreenivasa Rao, Bhatraju,Veerabhadra Swamy, Ponnapalli,Chandra, Sharad
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p. 303 - 306
(2007/10/03)
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- Synthesis and cytokine modulation properties of pyrrolo[2,3.d]-4- pyrimidone nucleosides
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A series of pyrrolo[2,3-d]pyrimidone nucleosides were synthesized and evaluated for their ability to enhance Type 2 cytokines and to suppress Type 1 cytokines in human T cells activated in vitro. Compounds 16b, 16c, 16d, 18c, and 19b induced substantial enhancement of IL-4 (a Type 2 cytokine) levels while three compounds (16b, 16c, and 16f) showed significant suppression of IFNγ (a Type 1 cytokine) levels. The results revealed a strict structural requirement for the nucleoside-mediated enhancement of IL- 4. Modifications of the ribofuranose moiety of the nucleosides either abolished or dramatically reduced the activity. Both the 5'-hydroxy and 5- carboxamidine are crucial for the activity. Of the few nucleoside analogues that demonstrated enhancement on Type 2 cytokine production, 7-(β-D- ribofuranosyl)pyrrolo[2,3d]-4-pyrimidone-5-carboxamidine (16c) showed a dramatic enhancement (> 200%) of IL-4 levels and a significant enhancement (36%) of IL-5 levels. Moreover, this compound showed substantial suppression of the Type 1 cytokines, IFNγ (42%), IL-2 (54%), and TNFα (55%). Similarly, compound 16b showed a substantial enhancement of IL-4 (46%) and suppression of IL-2 (35%), IFNγ (30%), and TNFα (26%). To our knowledge, these are the first nucleoside analogues that induce a Type 2 cytokine bias in T cells. The cytokine modulation property of 16c and 16b merits the therapeutic evaluation of these compounds in treating diseases in which immunopathology is associated with polarized Type 1 cytokine responses.
- Wang, Guangyi,Tam, Robert C.,Gunic, Esmir,Du, Jinfa,Bard, Josie,Pai, Bharati
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p. 2566 - 2574
(2007/10/03)
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- An Efficient Synthesis of 5-Deoxy-D-ribohexose
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5-Deoxy-D-ribohexose (1) has been obtained from methyl 2,3-O-isopropylidene-β-D-ribo-pentodialdo-1,4-furanoside via Wittig reaction with methoxymethylenetriphenyl phosphorane and subsequent hydrolytic and deprotection steps. 13C NMR spectrum show, that 1 occurs as two furanoses, two septanoses and an aldehydo form.Peracetylation of 5-deoxy-D-ribohexose leads to both furanose forms and, most probably, to an α-septanose ring.Key words: 5-deoxy-D-ribohexose, Wittig reaction
- Pakulski, Z.,Zamojski, A.
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p. 912 - 917
(2007/10/02)
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