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1.
Rakesh Kumar Edward E. Knaus Leonard I. Wiebe 《Journal of heterocyclic chemistry》1991,28(8):1917-1925
The regiospecific reaction of 5-vinyl-3′,5′-di-O-acetyl-2′-deoxyuridine ( 2 ) with HOX (X = Cl, Br, I) yielded the corresponding 5-(1-hydroxy-2-haloethyl)-3′,5′-di-O-acetyl-2′-deoxyuridines 3a-c . Alternatively, reaction of 2 with iodine monochloride in aqueous acetonitrile also afforded 5-(1-hydroxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3c ). Treatment of 5-(1-hydroxy-2-chloroethyl)- ( 3a ) and 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with DAST (Et2NSF3) in methylene chloride at -40° gave the respective 5-(1-fluoro-2-chloroethyl)- ( 6a , 74%) and 5-(1-fluoro-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6b , 65%). In contrast, 5-(1-fluoro-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6e ) could not be isolated due to its facile reaction with methanol, ethanol or water to yield the corresponding 5-(1-methoxy-2-iodoethyl)- ( 6c ), 5-(1-ethoxy-2-iodoethyl)- ( 6d ) and 5-(1-hydroxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3c ). Treatment of 5-(1-hydroxy-2-chloroethyl)- ( 3a ) and 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with thionyl chloride yielded the respective 5-(1,2-dichloroethyl)- ( 6f , 85%) and 5-(1-chloro-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6g , 50%), whereas a similar reaction employing the 5-(1-hydroxy-2-iodoethyl)- compound 3c afforded 5-(1-methoxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6c ), possibly via the unstable 5-(1-chloro-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine intermediate 6h . The 5-(1-bromo-2-chloroethyl)- ( 6i ) and 5-(1,2-dibromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6j ) could not be isolated due to their facile conversion to the corresponding 5-(1-ethoxy-2-chloroethyl)- ( 6k ) and 5-(1-ethoxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 61 ). Reaction of 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with methanolic ammonia, to remove the 3′,5′-di-O-acetyl groups, gave 2,3-dihydro-3-hydroxy-5-(2′-deoxy-β-D-ribofuranosyl)-furano[2,3-d]pyrimidine-6(5H)-one ( 8 ). In contrast, a similar reaction of 5-(1-fluoro-2-chloroethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6a ) yielded (E)-5-(2-chlorovinyl)-2′-deoxyuridine ( 1b , 23%) and 5-(2′-deoxy-β-D-ribofuranosyl)furano[2,3-d]pyrimidin-6(5H)-one ( 9 , 13%). The mechanisms of the substitution and elimination reactions observed for these 5-(1,2-dihaloethyl)-3′,5′-di-O-acetyl-2′-deoxyuridines are described. 相似文献
2.
Intramolecular cyclisation of properly protected and activated derivatives of 2′,3′-secouridine ( = 1-{2-hydroxy-1-[2-hydroxy-1-(hydroxymethyl)ethoxy]-ethyl}uracil; 1 ) provided access to the 2,2′-, 2,3′-, 2,5′-, 2′,5′-, 3′,5′-, and 2′,3′-anhydro-2′,3′-secouridines 5, 16, 17, 26, 28 , and 31 , respectively (Schemes 1–3). Reaction of 2′,5′-anhydro-3′-O-(methylsulfonyl)- ( 25 ) and 2′,3′-anhydro-5′-O-(methylsulfonyl)-2′,3′-secouridine ( 32 ) with CH2CI2 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene generated the N(3)-methylene-bridged bis-uridine structure 37 and 36 , respectively (Scheme 3). Novel chiral 18-crown-6 ethers 40 and 44 , containing a hydroxymethyl and a uracil-1-yl or adenin-9-yl as the pendant groups in a 1,3-cis relationship, were synthesized from 5′-O-(triphenylmethyl)-2′,3′-secouridine ( 2 ) and 5′-O,N6-bis(triphenylmethyl)-2′,3′-secoadenosine ( 41 ) on reaction with 3,6,9-trioxaundecane-1,11-diyl bis(4-toluenesulfonate) and detritylation of the thus obtained (triphenylmethoxy) methylcompound 39 and 43 , respectively (Scheme 4). 相似文献
3.
Dan Peters Anna-Britta Hrnfeldt Salo Gronowitz Nils Gunnar Johansson 《Journal of heterocyclic chemistry》1991,28(2):529-531
The Pd(0)-catalyzed coupling reaction of β-5-iodo-2′-deoxy-3′,5′-di-O-acetyluridine with various heteroaryltrimethylstannyl compounds gave the corresponding β-5-heteroaryl-2′-deoxy-3′,5′-di-O-acetyluridines in moderate yields. This direct coupling approach for nucleosides represented an interesting alternative to the 5-heteroaryl functionalization of pyrimidines followed by the Hilbert-Johnson glycosylation reaction which often yields mixtures of the α and β anomers. 相似文献
4.
The stereospecific cis-hydroxylation of 1-(2,3-dideoxy-β-D -glyceropent-2-enofuranosyl)thymine (1) into 1-β-D -ribofuranosylthymine (2) by osmium tetroxide is described. Treatment of 2′,3′-O, O-isopropylidene-5-methyl-2,5′-anhydrouridine (8) with hydrogen sulfide or methanolic ammonia afforded 5′-deoxy-2′,3′-O, O-isopropylidene-5′-mercapto-5-methyluridine (9) and 2′,3′-O, O-isopropylidene-5-methyl-isocytidine (10) , respectively. The action of ethanolic potassium hydroxide on 5′-deoxy-5′-iodo-2′,3′-O, O-isopropylidene-5-methyluridine (7) gave rise to the corresponding 1-(5-deoxy-β-D -erythropent-4-enofuranosyl)5-methyluracil (13) and 2-O-ethyl-5-methyluridine (14) . The hydrogenation of 2 and its 2′,3′-O, O-isopropylidene derivative 4 over 5% Rh/Al2O3 as catalyst generated diastereoisomers of the corresponding 5-methyl-5,6-dihydrouridine ( 17 and 18 ). 相似文献
5.
Jari Hovinen 《Helvetica chimica acta》1997,80(3):851-855
The 2′,3′-O-isopropylideneuridine ( 1 ) reacts with MeI in the presence of an excess of NaH in THF giving 2′,3′-O-isopropylidene-5′-O-methyluridine ( 2 ). Prolonged reaction time gives rise to 2′,3′-O-isopropylidene-3,5′-O-dimethyluridine ( 4 ). The use of an equimolar amount of base and alkylating agent results predominantly in methylation at N(3) (→ 3). 相似文献
6.
7.
8.
Evgeny I. Kvasyuk Tamara I. Kulak Igor A. Mikhailopulo Ramamurthy Charubala Wolfgang Pfleiderer 《Helvetica chimica acta》1995,78(7):1777-1784
The 5′-amino-5′-deoxy-2′,3′-O-isopropylideneadenosine ( 4 ) was obtained in pure form from 2′,3′-O-isopropylideneadenosine ( 1 ), without isolation of intermediates 2 and 3 . The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH2 functions of 4 (→7) . The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′-N-position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et3N (→ 5 ). The 3′-O-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′-O-deprotected compounds 8 and 9 , respectively, with (tert-butyl)dimethylsilyl chloride and 1H-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14 , respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH2Cl2. The trimeric (2′–5′)-linked adenylates 25 and 26 having the 5′-amino-5′-deoxyadenosine and 5′-deoxy-5′-(palmitoylamino)adenosine residue, respectively, at the 5′-end were prepared by the phosphoramidite method. Similarly, the corresponding 5′-amino derivatives 27 and 28 carrying the 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25–28 were 3-, 15-, 25-, and 34-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′–5′)ApApA. 相似文献
9.
The synthesis of 6-amino-1-(2′,3′-dideoxy-β-D -glycero-pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( =8-aza-7-deaza-2′,3′-dideoxyguanosine; 1 ) from its 2′-deoxyribofuranoside 5a by a five-step deoxygenation route is described. The precursor of 5a, 3a , was prepared by solid-liquid phase-transfer glyscosylation which gave higher yields (57%) than the liquid-liquid method. Ammonoloysis of 3b furnished the diamino nucleoside 3c . Compound 1 was less acid sensitive at the N-glycosydic bond than 2′,3′-dideoxyguanosine ( 2 ). 相似文献
10.
11.
An efficient synthesis of the unknown 2′-deoxy-D-threo-tubercidin ( 1b ) and 2′, 3′-dideoxy-3′-fluorotubercidin ( 2 ) as well as of the related nucleosides 9a, b and 10b is described. Reaction of 4-chloro-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine ( 5 ) with (tert-butyl)diphenylsilyl chloride yielded 6 which gave the 3′-keto nucleoside 7 upon oxidation at C(3′). Stereoselective NaBH4 reduction (→ 8 ) followed by deprotection with Bu4NF(→ 9a )and nucleophilic displacement at C(6) afforded 1b as well as 7-deaza-2′-deoxy-D-threo-inosine ( 9b ). Mesylation of 4-chloro-7-{2-deoxy-5-O-[(tert-butyl)diphenylsilyl]-β-D-threo-pentofuranosyl}-7H-pyrrolo[2,3-d]-pyrimidine ( 8 ), treatment with Bu4NF (→ 12a ) and 4-halogene displacement gave 2′, 3′-didehydro-2′, 3′-dideoxy-tubercidin ( 3 ) as well as 2′, 3′-didehydro-2′, 3′-dideoxy-7-deazainosne ( 12c ). On the other hand, 2′, 3′-dideoxy-3′-fluorotubercidin ( 2 ) resulted from 8 by treatment with diethylamino sulfurtrifluoride (→ 10a ), subsequent 5′-de-protection with Bu4NF (→ 10b ), and Cl/NH2 displacement. 1H-NOE difference spectroscopy in combination with force-field calculations on the sugar-modified tubercidin derivatives 1b , 2 , and 3 revealed a transition of the sugar puckering from the 3′T2′ conformation for 1b via a planar furanose ring for 3 to the usual 2′T3′ conformation for 2. 相似文献
12.
A series of thieno[3,2-d]pyrimidine-2,4-dione nucleosides modified in the carbohydrate moiety has been synthesized. In the first part, synthetic routes are described for the replacement of 5′-hydroxyl group in preformed 1-(β-D-ribofuranosyl)thieno[3,2-d]pyrimidine-2,4-dione I by fluoro, iodo or chloro atoms. Reduction of the 5′-iodo substituent of VI was then carried out catalytically using palladium on carbon as catalyst to give the expected 5′-deoxy derivative VIII. The lyxo-epoxide derivative XII was then synthesized by sequential treatment of the 5′-deoxy-5′-chloro derivative X with methanesulfonyl chloride and with sodium hydroxide. In the second part, most of attention has been devoted to apply different methods reported in the literature that allow access to 2′,3′-olefinic derivatives from the corresponding 2′,3′-dihydroxy precursor. The 5′-O-silyl protected bisxanthate XIV either on reduction with tri-n-butyltin hydride or by reductive elimination of the haloacetate XVI afforded the free 2′,3′-olefin nucleoside after removal of the 5′-protecting group. However none of the compounds in this series exhibited significant antiviral activity against HIV at the doses tested. 相似文献
13.
14.
J. W. Mcfarland B. M. Howe J. D. Lehmkuhler D. C. Myers 《Journal of heterocyclic chemistry》1995,32(6):1747-1750
Formylation of 2,2′,5′,2′-terfuran ( 1 ) with N-methylformanilide and phosphorus oxychloride gave 5-formyl-2,2′,5′,2′-terfuran ( 2 ) and 5,5′-diformyl-2,2′5′,2′-terfuran ( 3 ). Reduction of 2 and 3 afforded 5-hydroxymethyl-2,2′,5′,2′-terfuran ( 4 ) and 5,5′ dihydroxymethyl-2,2′,5′,2′-terfuran ( 5 ), respectively. Terfuran 1 reacted with phenylmagnesium bromide to give 5-(phenylhydroxymethyl)-2,2′,5′,2′-terfuran ( 6 ), and was carbonated to 5-carboxy 2,2′,5′,2′-terfuran ( 7 ) and 5,5′-dicarboxy-2,2′,5′,2′-terfuran ( 8 ). Bromination of 1 with N-bromosuccinimide gave 5,5′-dibromo 2,2′,5′,2′-terfuran ( 9 ). 相似文献
15.
The 1′,2′-unsaturated 2′,3′-secoadenosine and 2′,3′-secouridine analogues were synthesized by the regioselective elimination of the corresponding 2′,3′-ditosylates, 2 and 18 , respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, preferential elimination of the anomeric H–C(1′) in comparison to H? C(4′). The retained (tol-4-yl)sulfonyloxy group at C(3′) of 3 allowed the preparation of the 3′-azido, 3′-chloro, and 3′-hydroxy derivatives 5–7 by nucleophilic substitution. ZnBr2 in dry CH2Cl2 was found to be successful in the removal (85%) of the trityl group without any cleavage of the acid-sensitive, ketene-derived N,O-ketal function. In the uridine series, base-promoted regioselective elimination (→ 19 ), nucleophilic displacement of the tosyl group by azide (→ 20 ), and debenzylation of the protected N(3)-imide function gave 1′,2′-unsaturated 5′-O-trityl-3′-azido-secouridine derivative 21 . The same compound was also obtained by the elimination performed on 2,2′-anhydro-3′-azido-3′-azido-3′-deoxy-5′-O-2′,3′-secouridine ( 22 ) that reacted with KO(t-Bu) under opening of the oxazole ring and double-bond formation at C(1′). 相似文献
16.
A Practical Synthesis of 3′-Thioguanosine and of Its 3′-Phosphoramidothioite (a Thiophosphoramidite)
Starting from guanosine, an efficient method for the synthesis of 3′-thioguanosine (see 13 ) and of its 3′-phosphoramidothioite (see 23 ), suitable for automated incorporation into oligonucleotides, was developed. Reaction of 5′-N2-protected guanosine with 2-acetoxyisobutyryl bromide afforded stereoselectively the 2′-O-acetyl-3′-bromo-β-D -xylofuranosyl derivative 3 , which was converted to a 7 : 3 mixture of the S-acyl ribofuranosyl intermediates 5 or 6 and the 3′,4′-unsaturated by-product 4 . The S-acylated nucleosides 5 and 6 were then converted in three steps to 5′-O-(4,4′-dimethoxytrityl)-3′-S-(pyridin-2-ylthio)-3′-thioguanosine ( 11 ), which served as a common intermediate for the preparation of free 3′-thionucleoside 13 and 3′-thionucleoside 3′-phosphoramidothioite 23 . 相似文献
17.
Kay H. Boswell Leon F. Christensen Dennis A. Shuman Roland K. Robins 《Journal of heterocyclic chemistry》1975,12(1):1-9
A series of 6,8-disubstituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates were prepared employing preformed 9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate precursors. Three synthetic approaches were utilized to accomplish the syntheses. The first approach involved a study of the order of nucleophilic substitution, 6 vs 8, of the intermediate 6,8-dichloro-9-β-D-ribofuranosyipurine 3′,5′-cyclic phosphates ( 2 ) with various nucleophilic agents to yield 8-amino-6-chloro-, 8-chloro-6-(diethylamino)-, 6-chloro-8-(diethylamino)-, 6,8-bis-(diethylamino)- and 8-(benzylthio)-6-chloro-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate (4, 9, 10, 11, 13) respectively and 6-chloro-9-β-D-ribofuranosylpurin-8-one 3′,5′-cyclic phosphate ( 5 ) and 8-amino-9-β-D-ribofuranosylpurine-6-thione 3′,5′-cyclic phosphate ( 6 ). The order of substitution was compared to similar substitutions on 6,8-dichloropurines and 6,8-dichloropurine nucleosides. The second scheme utilized nucleophilic substitution of 6-chloro-8-substituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic, phosphates obtained from the corresponding 8-subslituted inosine 3′,5′-cyclic phosphates by phosphoryl chloride, 6,8-bis-(benzylthio)-, 6-(diethylamino)-8-(benzylthio),8-(p-chlorophenylthio(-6-(diethylamino)- and 6,8-bis-(methyl-thio)-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates ( 14, 12, 20 , and 21 ) respectively, were prepared in this manner. The final scheme involved N1-alkylation of an 8-substituted adenosine 3′,5′-cyclic phosphate followed by a Dimroth rearrangement to give 6-(benzylamino)-8-(methylthio)- and 6-(benzylamino)-8-bromo-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate ( 24 and 25 ). 相似文献
18.
John P. Paolini Frank P. Palopoli Louis J. Lendvay John Huffman 《Journal of heterocyclic chemistry》1987,24(3):549-553
The reaction of 2-aminopyridine, o-phthaldehydic acid and potassium cyanide gave pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one, which upon treatment with propargylbromide, yielded both O and N alkylated products. 2-Aminopyridine, o-phthaldehyde and potassium cyanide gave 1-cyano-2-(2-pyridyl)isoindole which rearranged in acid to give the previously unreported parent pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinole. Structures were confirmed using uv, ir, nmr and x-ray spectroscopy. 相似文献
19.
Harvey A. Itano 《Journal of heterocyclic chemistry》1974,11(6):1071-1073
9,10-Phenanthrenedione was reacted with equimolar amounts of N,N-dimethylguanidine or creatine in 0.2 N potassium hydroxide in ethanol-water, 7:3 to obtain 2′-(dimethylamino)spiro-[9H-fluorene-9,4′-[4H]imidazol]-5′(3′H)one or N-(3′,5′-dihydro-5′-oxospiro[9H-fluorene-9,4′-[4H]imidazol]-2′-yl)-N-methylglycine, respectively. These products are the first derivatives of this ring system with 2′-amino substituents. Formation of these products accounts for the previously reported absence of fluorescence when 9,10-phenanthrenedione reacts with N,N-di-substituted guanidines. 相似文献
20.
Cornelia Hrndler Wolfgang Pfleiderer Robert J. Suhadolnik Robert J. Suhadolnik Nicholas F. Muto Earl E. Henderson Earl E. Henderson Ming-Xu Guan 《Helvetica chimica acta》1997,80(3):767-785
An efficient strategy for the synthesis of (2′-5′)adenylate trimer conjugates with 2′-terminal 3′-O-(ω-hydroxyalkyl) and 3′-O-(ω-carboxyalkyl) spacers is reported. Npeoc-protected adenosine building blocks 37--40 for phosphoramidite chemistry carrying a 3′-O-[11-(levulinoyloxy)undecyl], 3′-O-{2-[2-(levulinoyloxy)ethoxy]ethyl}, 3′-O-[5-(2-cyanoethoxycarbonyl)pentyl], and 3′-O-{5-[(9H-fluoren-9-ylmethoxy)carbonyl]pentyl} moiety, respectively, were prepared (npeoc = 2-(4-nitrophenyl)ethoxycarbonyl). Condensation with the cordycepin (3′-deoxyadenosine) dimer 1 led to the corresponding trimers 42, 43, 47 , and 48. Whereas the levulinoyl (lev) and 9H-fluoren-9-ylmethyl (fm) blocking groups could be cleaved off selectively from the trimers 42, 43 , and 48 yielding the intermediates 44, 45 , and 49 for the synthesis of the 3′-O-(ω-hydroxyalkyl)trimers 53, 54 and the cholesterol conjugates 59--61 , the 2-cyanoethyl (ce) protecting group of 47 , however, could not be removed in a similar manner from the carboxy function. Trimer 47 served as precursor for the preparation of the trimer 55 with a terminal 3′-O-(5-carboxypentyl)adenosine moiety. The metabolically stable 3′-O-alkyl-(2′--5′)A derivatives were tested regarding inhibition of HIV-1 syncytia formation and HIV-1 RT activity. Only the conjugate 59 showed significant effects, whereas the trimers 53--55 and the conjugates 60 and 61 were less potent inhibitors, even at 100-fold larger concentrations. 相似文献