- Acyclovir preparation device and preparation method
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The invention discloses an acyclovir preparation device which comprises a condensation reaction device, a purification and impurity removal device and an esterification reaction device. The acyclovir preparation method comprises the following steps: preheating a pipeline to a reaction temperature, carrying out a condensation reaction, carrying out purification and impurity removal, carrying out an esterification reaction, and the like. According to the acyclovir preparation device and method disclosed by the invention, a tank reaction can be replaced with a continuous tube reaction, the reaction conditions are mild, and the yield is high; and feed liquids in the after-treatment process can be recycled, emissions of three wastes are reduced, after-treatment difficulties are reduced, and the device and method are green and environment-friendly.
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Page/Page column 7-11
(2019/10/04)
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- Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors
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New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25).
- Puig-De-La-Bellacasa, Raimon,Gimenez, Laura,Pettersson, Sofia,Pascual, Rosalia,Gonzalo, Encarna,Este, Jose A.,Clotet, Bonaventura,Borrell, Jose I.,Teixido, Jordi
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scheme or table
p. 159 - 174
(2012/09/05)
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- Novel 5-(N -alkylaminouracil) acyclic nucleosides
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Protocols for the two-step syntheses of new 5-(N-hydroxyalkyl- and 5-N-benzylamino)uracil acyclic nucleosides bearing various functional groups (alkoxy/hydroxy and cyano/ester) are presented. Two groups of the title compounds were synthesised via aminolysis of 5-bromouracil and, subsequently, either coupling with an alkylating agent (2-chloromethoxyethyl acetate), or Michael-type addition to acrylonitrile/methyl acrylate. The reverse sequences for both syntheses were also studied. The target molecules were designed as non-nucleoside reverse transcriptase inhibitors (NNRTI) and are analogues of 1-(hydroxyethoxymethyl)-6-thiophenylthymine (HEPT) and 3-benzyl-1- cyanomethyluracils. The obtained compounds will be used in screening tests for anti-HIV-1 activity. Georg Thieme Verlag Stuttgart New York.
- Boncel, Sawomir,Gondela, Andrzej,McZka, MacIej,Tuszkiewicz-Kuznik, Magdalena,Grec, Przemysaw,Hefczyc, Barbara,Walczak, Krzysztof
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experimental part
p. 603 - 610
(2011/04/12)
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- Synthesis of oligoribonucleotides containing pyrimidine 2′-O-[(hydroxyalkoxy)methyl]ribonucleosides
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A simple and efficient method for the preparation of pyrimidine 2′-O-[(2-hydroxyethoxy)methyl]ribonucleosides and 2′-O-[(3- hydroxypropoxy)methyl]ribonucleosides has been developed. These modified nucleosides were incorporated into oligoribonucleotides, which were shown to form stable RNA/RNA duplexes.
- Bobkov, Georgii V.,Brilliantov, Kirill V.,Mikhailov, Sergey N.,Rozenski, Jef,Van Aerschot, Arthur,Herdewijn, Piet
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p. 804 - 819
(2008/02/02)
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- Synthesis of analogs of L-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells
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L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepT1) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity of L-valacyclovir for PepT1 is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions of L-valacyclovir with PepT1, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepT1 in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepT1 in binding studies, but only the purine analog (as the L-valine ester) showed PepT1-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepT1.
- Friedrichsen, Gerda Marie,Chen, Weiqing,Begtrup, Mikael,Lee, Chao-Pin,Smith, Philip L.,Borchardt, Ronald T.
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- Process for producing purine derivatives
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Purine derivatives in which a desired substituent is introduced into the 9-position only are synthesized by first introducing an easily-removable substituent in the 7-position of a purine base of natural purine nucleosides obtained through fermentation or derivatives thereof, then hydrolyzing the ribose moiety to form purine derivatives having the substituent in the 7-position, subsequently introducing the desired substituent in the 9-position, and then removing the substituent in the 7-position.
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- Process for producing acyclic nucleosides and process for separating purine nucleosides
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Herein is disclosed a novel and industrially advantageous process for synthesizing acyclic nucleosides such as acyclovir and ganciclovir from ribonucleosides, which process comprises adding an acid catalyst and an acid anhydride to a solution of a ribonucleoside such as guanosine and an ester derivative of an acyclic sugar, and heating the mixture, whereby a transglycosilation reaction takes place between the ribose moiety of the ribonucleoside and the ester derivative of the acyclic sugar. Herein is also disclosed an industrially favorable method for the separation of 9-substituted purine nucleosides which are important intermediates for the synthesis of acyclic nucleosides such as acyclovir, ganciclovir, and the like from ribonucleosides, which method comprises crystallizing only the 9-isomer from a solution or suspension containing both a 9-substituted purine nucleoside and a 7-substituted purine nucleoside by cooling the solution or/and by adding a crystallizing solvent thereto.
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- Hydroxyalkylammonium-pyrimidines or purines and nucleoside derivatives, useful as inhibitors of inflammatory cytokines
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Novel hydroxyalkylammonium-pyrimidine of the formula STR1 and nucleoside derivatives have been found to be useful as inhibitors of inflammatory cytokines. They can be used, inter alia, in the therapy of septic shock, cachexia, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and AIDS. The compounds are typically prepared by reaction of an iodo substituted nucleoside with the appropriately substituted hydroxyalkylamine.
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- Synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine
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A convenient synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine by chemical transpurination was developed. The isomerization of the 7-isomer to the desired 9-isomer and the purification of the 9- isomer was achieved simply by concentration, heating and further crystallization.
- Shiragami,Koguchi,Tanaka,Takamatsu,Uchida,Ineyama,Izawa
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p. 337 - 340
(2007/10/02)
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- Process for the preparation of acylals
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Compounds of the formula STR1 can advantageously be prepared by reacting compounds the formula II STR2 in which the substituents R1 -R4 have the meanings given, with the anhydride of the formula III STR3 in the presence of dimethyl sulfoxide and the acid corresponding to the anhydride of the formula III.
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