- From adenosine to 3′-deoxyadenosine: Development and scale up
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A manufacturing process has been developed suitable for the production of 3′-deoxyadenosine (cordycepin, 3′-dA) in 20% yield from adenosine. The chemistry involves conversion of adenosine to isomeric 2′,3′-bromoacetates with isolation of the desired isomer in high purity. Acidic hydrolysis followed by hydrogenolysis afforded product with a purity of ≥99%. Unlike routes reported in the literature, intermediates are isolated as solids, thus avoiding the use of chromatography for isomer separation and final product purification.
- Aman, Sayed,Anderson, D. Jason,Connolly, Terrence J.,Crittall, Andrew J.,Ji, Guijun
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Read Online
- A NUCLEOSIDE DERIVATIVE FROM EMERICELLA NIDULANS
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5'-Acetyl-3'-deoxyadenosine, a new nucleoside derivative, has been isolated from Emericella nidulans var. lata, together with 3'-deoxyadenosine (cordycepin). Key Word Index: Emericella nidulans; Ascomycotina; fungus; nucleoside; 5'-acetyl-3'-deoxyadenosine; 3'-deoxyadenosine.
- Kawahara, Nobuo,Sekita, Setsuko,Satake, Motoyoshi,Udagawa, Shun-Ichi
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Read Online
- REGIOSPECIFIC AND STEREOSELECTIVE CONVERSION OF RIBONUCLEOSIDES TO 3-DEOXYNUCLEOSIDES. A HIGH YIELD THREE-STAGE SYNTHESIS OF CORDYCEPIN FROM ADENOSINE.
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Treatment of 2',3'-anhydroadenosine (obtained in 92percent yield from adenosine) with lithium triethylborohydride (or deuteride) gave cordycepin (or its 3'(R)-deuterio derivative) in 90percent overall yields with no 2'-deoxy isomer detected.
- Hansske, Fritz,Robins, Morris J.
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Read Online
- Synthesis method of cordycepin
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The invention discloses a synthetic method for cordycepin. The method comprises the following steps: with adenosine as a starting material, subjecting adenosine and Mattock's bromide to bromination in a reaction solvent of acetonitrile and/or ethyl acetate during implementation of hydroxyl protection so as to obtain two products, i.e., 5'-[2,5,5-trimethyl-1,3-dioxolane-4-one-2-yl]-3'-bromo-3'-deoxy-2'-O-acetyl adenosine and 5'-[2,5,5-trimethyl-1,3-dioxolane-4-one-2-yl]-2'-bromo-2'-deoxy-3'-O-acetyl adenosine; then removing protective groups so as to obtain 3'-bromo-3'-deoxy-adenosine hydrochloride; and subjecting 3'-bromo-3'-deoxy-adenosine hydrochloride to debromination so as to obtain 3'-deoxyadenosine, i.e., cordycepin. The synthetic method provided by the invention is simple to operate, has short reaction steps and does not need purification in the process of reaction; and the purity and each index of the obtained cordycepin product are better than a currently commercially available cordycepin product.
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Paragraph 0022; 0023; 0033-0037
(2020/07/13)
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- An effective and convenient synthesis of cordycepin from adenosine
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Cordycepin is a purine nucleoside analog with potent and diverse biological activities. Herein, we designed two methods to synthesize cordycepin. One method mainly converted the 3′-OH group into an iodide group and further dehalogenation to yield the final product. Although this method presented a short synthetic procedure, the synthesis had a low overall yield, resulting in only 13.5% overall yield. To improve the overall yield of cordycepin, another synthetic route was studied, which consisted of four individual steps: (1) 5′-OH protection (2) esterification (3) -O-tosyl (-OTs) group removal (4) deprotection. The key step in the synthetic method involved the conversion of 5′-O-triphenylmethyladenosine to 3′-O-tosyl-5′-O-triphenylmethyladenosine, using LiAlH4 as reducing agent. The main advantages of this route were an acceptable total product yield and the commercial availability of all starting materials. The optimal reaction conditions for each step of the route were identified. The overall yield of cordycepin obtained from adenosine as the starting material was 36%.
- Huang, Shen,Liu, Hui,Sun, Yanhua,Chen, Jian,Li, Xiufang,Xu, Jiangfeng,Hu, Yuwei,Li, Yuqing,Deng, Zhiwei,Zhong, Shian
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p. 149 - 160
(2018/01/17)
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- Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
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The disclosed invention is a composition for and a method of seating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
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- ADENOSINE ANALOG AND ITS USE IN REGULATING THE CIRCADIAN CLOCK
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Provided are a kind of nucleoside analogue compounds, and compositions comprising these compounds and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via these compounds or the compositions.
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Paragraph 0113; 0126; 0127
(2018/08/12)
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- Preparation method of cordycepin
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The invention discloses a preparation method of cordycepin. The preparation method comprises the following steps: a formula is shown in the description, wherein X is Cl or Br; R1 is one of the following groups: formulas are shown in the description; R2 is one of the following groups: formulas are shown in the description. The preparation method disclosed by the invention takes easy-to-obtain adenosine as a starting raw material and is simple to operate and convenient for purification and industrial large-scale production is easy to realize.
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Paragraph 0074-0078
(2018/11/03)
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- Phosphorus pentachloride promoted gem-dichlorination of 2′- and 3′-deoxynucleosides
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Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a gem-dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus pentachloride to suitably protected 2′- or 3′-ketodeoxynucleoside intermediates as the key step, facilitating the rapid construction of such functionalized molecules. Under the same reaction conditions, the highest chemoselectivity was observed for the formation of 2′,2′-dichloro-2′,3′-dideoxynucleosides, while a competing 2′,3′-elimination process occurred in the case of the 3′,3′-dichloro counterparts.
- Da Paixao Soares, Fabio,Groaz, Elisabetta,Herdewijn, Piet
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- The Chemoenzymatic Synthesis of 2-Chloro- and 2-Fluorocordycepins
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Two approaches to the chemoenzymatic synthesis of 2-fluorocordycepin and 2-chlorocordycepin were studied: (i) the use of 3′-deoxyadenosine (cordycepin) and 3′-deoxyinosine (3′dIno) as donors of 3-deoxy- d -ribofuranose in the transglycosylation of 2-fluoro- (2F Ade) and 2-chloroadenine (2Cl Ade) catalyzed by the recombinant E. coli purine nucleoside phosphorylase (PNP), and (ii) the use of 2-fluoroadenosine and 3′-deoxyinosine as substrates of the cross-glycosylation and PNP as a biocatalyst. An efficient method for 3′-deoxyinosine synthesis starting from inosine was developed. However, the very poor solubility of 2Cl Ade and 2F Ade is the limiting factor of the first approach. The second approach enables this problem to be overcome and it appears to be advantageous over the former approach from the viewpoint of practical synthesis of the title nucleosides. The 3-deoxy-α- d -ribofuranose-1-phosphate intermediary formed in the 3′dIno phosphorolysis by PNP was found to be the weak and marginal substrate of E. coli thymidine (TP) and uridine (UP) phosphorylases, respectively. Finally, one-pot cascade transformation of 3-deoxy- d -ribose in cordycepin in the presence of adenine and E. coli ribokinase, phosphopentomutase, and PNP was tested and cordycepin formation in ca. 3.4% yield was proved.
- Denisova, Alexandra O.,Tokunova, Yulia A.,Fateev, Ilja V.,Breslav, Alexandra A.,Leonov, Vladimir N.,Dorofeeva, Elena V.,Lutonina, Olga I.,Muzyka, Inessa S.,Esipov, Roman S.,Kayushin, Alexey L.,Konstantinova, Irina D.,Miroshnikov, Anatoly I.,Stepchenko, Vladimir A.,Mikhailopulo, Igor A.
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p. 4853 - 4860
(2017/10/06)
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- Synthetic method for 3-deoxyadenosine and product thereof, and application of product
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The invention relates to a synthetic method for compound, especially to a synthetic method for 3-deoxyadenosine and a product thereof, and application of the product. The synthetic method comprises the following steps: (1) halogenation of adenosine: with tetraacetoxysilane as a halogenation catalyst, synthesizing 3(2)-deoxy-3(2)-halogeno-2(3),5-di(O-acetyl)adenosine from a system consisting of phosphorus trichloride and tetraacetoxysilane; (2) recrystallization and purification: carrying out purification and separation by using absolute ethyl alcohol so as to obtain a pure 3(2)-deoxy-3(2)-halogeno-2(3),5-di(O-acetyl)adenosine crystal; and (3) catalytic hydrogenation: carrying out catalytic hydrogenation so as to obtain 3-deoxyadenosine. According to the invention, 3(2)-deoxy-3(2)-halogeno-2(3),5-di(O-acetyl)adenosine is obtained through selection of an appropriate halogenation reagent, and cyclization and ring-opening reactions are avoided, so procedures are reduced and cost is lowered; and 3-deoxyadenosine with high purity is prepared.
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Paragraph 0019
(2017/05/27)
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- NEW 2' AND/OR 5' AMINO-ACID ESTER PHOSPHORAMIDATE 3'-DEOXY ADENOSINE DERIVATIVES AS ANTI-CANCER COMPOUNDS
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The present invention relates to chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours inhomo sapiens. The compounds are derivatives of cordycepin (3'-deoxyadenosine) having a 2' and/or 5'- amino-acid ester phosphoramidate moeity.
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- Structure-activity relationships of synthetic cordycepin analogues as experimental therapeutics for African trypanosomiasis
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Novel methods for treatment of African trypanosomiasis, caused by infection with Trypanosoma brucei are needed. Cordycepin (3′-deoxyadenosine, 1a) is a powerful trypanocidal compound in vitro but is ineffective in vivo because of rapid metabolic degradation by adenosine deaminase (ADA). We elucidated the structural moieties of cordycepin required for trypanocidal activity and designed analogues that retained trypanotoxicity while gaining resistance to ADA-mediated metabolism. 2-Fluorocordycepin (2-fluoro-3′-deoxyadenosine, 1b) was identified as a selective, potent, and ADA-resistant trypanocidal compound that cured T. brucei infection in mice. Compound 1b is transported through the high affinity TbAT1/P2 adenosine transporter and is a substrate of T. b. brucei adenosine kinase. 1b has good preclinical properties suitable for an oral drug, albeit a relatively short plasma half-life. We present a rapid and efficient synthesis of 2-halogenated cordycepins, also useful synthons for the development of additional novel C2-substituted 3′-deoxyadenosine analogues to be evaluated in development of experimental therapeutics.
- Vodnala, Suman K.,Lundb?ck, Thomas,Yeheskieli, Esther,Sj?berg, Birger,Gustavsson, Anna-Lena,Svensson, Richard,Olivera, Gabriela C.,Eze, Anthonius A.,De Koning, Harry P.,Hammarstr?m, Lars G. J.,Rottenberg, Martin E.
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p. 9861 - 9873
(2014/01/17)
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- Structure-activity relationship of adenosine 5′-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: Rational design of antagonists
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Adenosine 5′-diphosphoribose (ADPR) activates TRPM2, a Ca 2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure-activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2′-deoxy-ADPR (86, IC50 = 3 μM), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfamate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
- Moreau, Christelle,Kirchberger, Tanja,Swarbrick, Joanna M.,Bartlett, Stephen J.,Fliegert, Ralf,Yorgan, Timur,Bauche, Andreas,Harneit, Angelika,Guse, Andreas H.,Potter, Barry V. L.
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p. 10079 - 10102
(2014/01/17)
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- Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
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2′-Deoxy, 3′-deoxy, and 2′,3′-dideoxyribosyl surrogates of isoleucyl and methionyl sulfamate adenylates have been investigated to identify the pharmacophoric importance of the ribose group for the inhibition of Escherichia coli methionyl-tRNA (MRS) and isoleucyl-tRNA (IRS) synthetases. Molecular modeling of 2′,3′-dideoxyribosyl Met-NHSO2-AMP (9) with the crystal structure of E. coli MRS revealed that the lack of the two hydroxyl groups on ribose was compensated by the formation of an extra hydrogen bond between the ring oxygen and His24, resulting in a small activity reduction.
- Sung, Eun Kim,Su, Yeon Kim,Kim, Sunghoon,Kang, Taehee,Lee, Jeewoo
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p. 3389 - 3393
(2007/10/03)
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- Process for the preparation of 9-beta-anomeric nucleoside analogs
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A process for substantially enhancing the regio and stereoselective synthesis of 9-β-anomeric nucleoside analogs is described. The introduction of the sugar moiety onto a 6-substituted purine base was preformed so that only the 9-β-D- or L-purine nucleoside analogs were obtained. This regio and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs and in particular 2′-deoxy, 3′-deoxy, 2′-deoxy-2′-β-fluoro and 2′,3′-dideoxy-2′-β-fluoro purine nucleoside analogs in high yield without virtually any formation of the 7-positional isomers. The compounds are drugs or intermediates to drugs.
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- COMPOUNDS RESISTANT TO METABOLIC DEACTIVATION AND METHODS OF USE
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Therapeutic compounds having increased resistance to deamination and inactivation by metabolic enzymes are provided. The compounds include nucleotide analogs and nucleotide analogs, derivatized with aminal and/or thioaminal groups to prevent deamination of free amine. The compounds can be used in a variety of treatments, including treatment of neoplastic disorders, infections from fungal or fungal like organisms, and infections from parasites.
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- New synthesis of 3′-deoxypurine nucleosides using samarium(III) iodide complex
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Regio- and stereoselective iodinative cleavage of 2′,3′ -anhydropurine nucleosides was achieved with samarium diiodide and ethyl bromoacetate to produce the corresponding 3′-iodopurine nucleosides, which were then converted to 3′-deoxypurine nucleosides including the natural product cordycepin.
- Kwon, Doo Won,Jeon, Jae-Ho,Kang, Changwon,Kim, Yong Hae
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p. 7941 - 7943
(2007/10/03)
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- Anti-HCV nucleoside derivatives
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The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
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- Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
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The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (""RT-PCR""). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
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- Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
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The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.
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- Nucleic acid related compounds. 101. S-adenosyl-L-homocysteine hydrolase does not hydrate (5'-fluoro)vinyl or (6'-halo)homovinyl analogues derived from 3'-deoxyadenosine or 3'-(chloro or fluoro)-3'-deoxyadenosine
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S-Adenosyl-L-homocysteine (AdoHcy) hydrolase is crucial for the maintenance of biomethylation. The usual mechanistic sequence involves oxidation of AdoHcy at C3' followed by elimination of L-homocysteine, Michael addition of water, and reduction to give adenosine. A 6'- fluorohomovinyladenosine analogue (EDDFHA) undergoes hydration of the 5',6' double bond (hydrolytic activity) at a more rapid rate than oxidation at C3'. Three 4',5'-didehydro-5'-deoxy-5'-fluoro nucleoside analogues were prepared from 3'-deoxy- and 3'-(chloro and flouro)-3'-deoxyadenosine via generation of the vinyl fluorides by thermolysis of 5'-fluoro-5'-thioether sulfoxides. The 3'-deoxy analogues of 6'-halohomovinyladenosines were prepared by Wittig extension with a 3'-deoxy-5'-carboxaldehyde and halodestannylation of vinyl stannanes. The 3'-hydroxyl group appears to be essential for binding to AdoHcy hydrolase. No hydrolytic activity at C5', or C6' was observed with the nonoxidizable 3'-deoxy or 3'-(chloro or fluoro) analogues in contrast with their 3'-hydroxy counterparts (ZDDFA and EDDFHA). These 3'-modified analogues cannot reduce enzyme-bound NAD+ to NADH and do not produce time-dependent inhibition for AdoHcy hydrolase, but are weak competitive inhibitors (K(i) = 150-200 μM).
- Robins,Neschadimenko,Ro,Yuan,Borchardt,Wnuk
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p. 1205 - 1211
(2007/10/03)
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- Synthesis of 2′,3′-dideoxypurinenucleosides via the palladium catalyzed reduction of 9-(2,5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)purine derivatives
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Practical method to produce 2′,3′-dideoxypurinenucleosides from 9-(2,5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)purines (1) was developed. High ratio of 2′,3′-dideoxynucleoside to 3′-deoxyribonucleoside was obtained by selecting the reaction conditions (solvent, pH and/or base), or changing 2′-acyloxy leaving group. The reaction mechanism was studied by deuteration experiments of 1a and 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (12).
- Shiragami, Hiroshi,Amino, Yusuke,Honda, Yutaka,Arai, Masayuki,Tanaka, Yasuhiro,Iwagami, Hisao,Yukawa, Toshihide,Izawa, Kunisuke
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- Asymmetric synthesis of nucleosides via molybdenum-catalyzed alkynol cycloisomerization coupled with stereoselective glycosylations of deoxyfuranose glycals and 3-amidofuranose glycals
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Deoxygenated furanose glycals were efficiently prepared by molybdenum pentacarbonyl-catalyzed cycloisomerization of alkynyl alcohols, which were easily prepared in chiral nonracemic form by short synthetic sequences featuring asymmetric epoxidations of commercially available allylic alcohols. The cycloisomerization reaction was demonstrated to be compatible with ester and amide functional groups. A 2,3-dideoxyfuranose glycal was stereoselectively converted into the anti-AIDS β-nucleoside stavudine (2',3'-didehydro-2',3'-dideoxythymidine, d4T) and the antiviral 3'-deoxy-β-nucleoside cordycepin. The anchimeric and hydrogen-bond-directing effects of 3-amido-2,3-dideoxyfuranose glycals were exploited in a novel and highly stereoselective synthesis strategy for a variety of biologically active 3'-amino-2',3'-dideoxy- and 3'-amino-3'-deoxy-β-nucleosides, including puromycin aminonucleoside. In addition, the mechanism of the molybdenum-catalyzed alkynol cycloisomerization reaction has been studied. Evidence is presented which indicates that cyclic molybdenum carbene anions are catalytic intermediates in these cyclizations.
- McDonald, Frank E.,Gleason, Mark M.
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p. 6648 - 6659
(2007/10/03)
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- Nucleic Acid Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2',3'-Anhydro, 2'(and 3')-Deoxy, 2',3'-Didehydro-2',3'-dideoxy, and 2',3'-Dideoxynucleoside Analogues
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Treatment of purine, pyrimidine, and modified purine (antibiotic) ribonucleosides with 2-acetoxy-2-methylpropanoyl (α-acetoxyisobutyryl) bromide in acetonitrile gave mixtures of 2',3'-bromohydrin acetates with different O5' substituents.Significant amounts of 5'-unprotected (hydroxyl) bromo acetates were obtained in some cases, and formation of 2',3'-O-isopropylidene derivatives as minor byproducts was detected for the first time.Acid-catalyzed nucleophilic displacement of chloride by bromide occurred with 2-amino-6-chloropurine riboside, but no substitution of fluoride by bromide was detected with 6-amino- 2-fluoropurine riboside.Treatment of the trans bromo acetate mixtures obtained from purine-type nucleosides with Dowex 1 x 2 (OH(-)) in methanol gave the 2',3'-anhydro (ribo epoxide) compounds.Radical-mediated hydrogenolytic debromination and deprotection gave 2'- and 3'-deoxynucleosides.Treatment of the bromo acetate mixtures with zinc-copper couple or acetic acid-activated zinc effected reductive elimination, and deprotection gave 2',3'-didehydro-2',3'-dideoxy compounds which were hydrogenated to give 2',3'-dideoxynucleosides.A number of these analogues have potent inhibitory activity against AIDS and hepatitis B viruses.New 13C NMR data for several types of unsaturated-sugar nucleosides are tabulated.These procedures are directly applicable for the preparation of L-didehydro-dideoxy and L-dideoxy nucleoside analogues.
- Robins, Morris J.,Wilson, John, S.,Madej, Danuta,Low, Nicholas H.,Hansske, Fritz,Wnuk, Stanislaw F.
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p. 7902 - 7908
(2007/10/03)
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- Asymmetrische Synthese von Stavudin (d4T) und Cordycepin durch Cycloisomerisierung von Alkinylalkoholen zu endocyclischen Enolethern
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Stichworte: Asymmetrische Synthesen * Cyclisierungen * Nucleoside
- McDonald, Frank E.,Gleason, Mark M.
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p. 356 - 358
(2007/10/02)
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- Nucleosides. Part LVI. Aminolysis of carbamates of adenosine and cytidine
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The 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group, introduced 1984 as protecting group for exocyclic amino functions of nucleic-acid bases, reacts with amines under mild conditions to urea derivatives. Treatment of 2',5'-di-O-acetyl-N6-[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin (3) with NH3/MeOH overnight at room temperature affords cordycepin (4) and N6-carbamoylcordycepin (5). Preliminary investigations towards the elucidation of the reaction mechanism indicate that the aminolysis proceeds via an addition-elimination or an isocyanate mechanism, depending on the reaction conditions. The phenoxycarbonyl (phoc) group at N6 or N4 was chosen to study the mild conversion of carbamates with aromatic amines into ureas of adenosine and cytidine, respectively.
- Sigmund,Pfleiderer
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p. 1267 - 1280
(2007/10/02)
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- Synthesis and antifungal activity of 3'-deoxyribonucleosides
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Synthesis and antifungal activity of 3'-deoxyribonucleosides containing naturally occurring pyrimidine and purine bases are reported.
- Kumar,Khan,Manglani,Khan,Katti
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p. 1049 - 1058
(2007/10/02)
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- REACTION OF ADENINE NUCLEOSIDES, TOSYLATED IN THE CARBOHYDRATE MOIETY, WITH LITHIUM TRIETHYLBOROHYDRIDE
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The reaction of lithium triethylborohydride with the 2',3'-di-O-p-tolylsulphonyl derivatives of 9-β-D-ribofuranosyladenine, 9-β-D-arabinofuranosyladenine, 9-β-D-xylofuranosyladenine and 9-β-D-lyxofuranosyladenine was studied.The reaction of 2',3'-di-O-p-tolylsulphonyladenosine with LiEt3BH gave 9-(3-deoxy-β-D-threo-pentofuranosyl)adenine.This rearrangement reaction was used for the synthesis of 9-(3,5-dideoxy-β-D-threo-pentofuranosyl)adenine in one step from 2',3',5'-tri-O-p-tolylsulphonyladenosine in 58percent yield.The p-tolylsulphonyl group in the 2'-"up" configuration of unprotected adenine nucleosides was preferentially attacked by LiEt3BH giving S-O-bond scission.This was shown by the formation of 9-(3-deoxy-β-D-threo-pentofuranosyl)adenine from 2',3'-di-O-p-tolylsulphonyl-9-β-D-arabinofuranosyladenine and by the formation of 9-β-D-lyxofuranosyladenine from 2'-O-p-tolylsulphonyl-9-β-D-lyxofuranosyladenine with LiEt3BH. 9-β-D-Lyxofuranosyladenine was synthesized from 3',5'-di-O-benzoyl-9-β-D-xylofuranosyladenosine in 88percent yield using a triflate displacement reaction.
- Herdewijn, Piet
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p. 6563 - 6580
(2007/10/02)
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- SYNTHETIC STUDIES ON BIOLOGICALLY ACTIVE NATURAL PRODUCTS BY A CHEMICOENZYMATIC APPROACH. ENANTIOSELECTIVE SYNTHESIS OF C- AND N-NUCLEOSIDES, SHOWDOMYCIN, 6-AZAPSEUDOURIDINE AND CORDYCEPIN
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An efficient synthesis of C- and N-nucleosides has been developed in an enantioselective and stereocontrolled manner starting from Diels-Alder adduct of furan and dimethyl acetylenedicarboxylate by chemicoenzymatic strategy.The symmetric unsaturated dimethyl esters 2 and 3 were almost quantitatively hydrolysed with pig liver esterase to yield half-esters 4 and 5 with reasonably high optical yields.Decarboxylative ozonolysis of the chiral half-esters 4 followed by chemical transformation afforded methyl-L-riboside 12, but after the enantiomer conversion (4 to 13 and 5 to 28) the methyl D-riboside (17), (+)-showdomycin (22), and (-)-6-azapseudouridine (27), were obtained from 13, and (-)-cordycepin (32) was obtained from 28.
- Ohno, Masaji,Ito, Yukishige,Arita, Masafumi,Shibata, Tomoyuki,Adachi, Kunitomo,Sawai, Hiroaki
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p. 145 - 152
(2007/10/02)
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- Process for deoxygenating secondary alcohols
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The process for removing a secondary hydroxyl group from an organic compound having at least one secondary hydroxyl group and having any amino groups protected, comprises the reaction of a reactive ester of said secondary hydroxyl group selected from the group consisting of an O-alkylthioester and an O-alkylselenoester with at least one mole of an organotin hydride, preferably tri-n-butylstannane, in an inert, aprotic solvent at a temperature of at least about 100° C and under an inert atmosphere. The process is particularly useful in removing secondary alcohols in aminoglycoside antibiotics to produce deoxy derivatives thereof having antibacterial activity. Also described are novel O-sec.-alkylthiobenzoate, O-sec.-alkyl-S-methylxanthate, N-(sec.-alkoxythiocarbonyl)-imidazole esters, and di-O-alkylthiocarbonates having at least one secondary O-alkyl group, useful intermediates of the claimed process.
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