嘧啶并呋咱核苷衍生物的制备及其活性初探

4H,6H-[1,2,5]噁二唑并[3,4-d]嘧啶-5,7-二酮1-氧化物(1)和6-甲基-4H,6H-[1,2,5]噁二唑并[3,4-d]嘧啶-5,7-二酮1-氧化物(2)是一氧化氮(NO)供体, 将它们分别在无溶剂条件下与高温熔融的全乙酰基保护的核糖、木糖、葡萄糖进行糖基化反应, 分别得到相应的噁二唑并[3, 4-d]嘧啶核苷类化合物7, 9～12, 化合物7经NH₃-MeOH处理, 去O-乙酰基制得8, 这些新型核苷化合物可作为潜在的NO供体. 部分此类化合物的生物活性研究表明, 嘧啶并呋咱核苷衍生物具有抗病毒、抗肿瘤活性, 为研究抗病毒、抗肿瘤药物提供了新结构类型的候选化合物.     

Synthesis of 2H-pyrano[2,3-d]pyrimidine derivatives

Two series of 2H-pyrano[2,3-d]pyrimidine-2,5(6H)-dione derivatives have been prepared. Thus, the reaction of 6-hydroxy-pyrimidin-4(3H)-ones (1 a–c) with bis-2,4,6-trichlorphenyl malonates (2 a–d) or diethyl malonates (3 a–d) afforded good yields of 4-hydroxy-2H-pyrano[2,3-d]pyrimidine-2,5(6H)-diones (4 a-l). Application of our modifiedPechmann reaction^9–11 using -aminocrotonate (5) or -keto esters (6, 7) in the presence of ammonium acetate yielded the 2H-pyrano[2,3-d]pyrimidinediones8 a–h.Dedicated to Prof. Dr.Karl Schlögl, University of Vienna, on the occasion of his 60th birthday.     

DMF acetals as alkylating and cyclizing agents: A facile route to substituted pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones

Summary Several 7-methyl-5-alkyl-2-vinylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones were prepared. The successful cyclization and alkylation of 6-(-methylbenzylidenehydrazino)-1-methyluracils2a–d using dimethylformamide acetals at high temperature provided6a–d,7a–d, and8a–d. Treatment of6a–d and7a–d with acid afforded 7-methyl-5-alkylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones9a,b; under the same conditions,3a–d reacted to 7-methylpyrazolo[3,4-d]-pyrimidine-4,6(5H)-dione (4) in good yield.

---

DMF-Acetale als Alkylierungs- und Ringschlußreagentien: ein einfacher Weg zu substituierten Pyrazolo[3,4-d]pyrimidin-4,6(5H,7H)-dionen

Zusammenfassung Es wurden verschiedene 7-Methyl-5-alkyl-2-vinylpyrazolo[3,4-d]pyrimidin-4,6(5H,7H)-dione hergestellt. Cyclisierung und Alkylierung der 6-(-Methylbenzylidenhydrazino)-1-methyl-uracile2a–d mit Hilfe von Dimethylformamidacetalen bei hohen Temperaturen ergab6a–d,7a–d und8a–d. Behandlung von6a–d und7a–d mit Säure lieferte die 7-Methyl-5-alkylpyrazolo[3,4-d]pyrimidin-4,6(5H,7H)-dione9a,b; unter den gleichen Bedingungen reagierten3a–d in guter Ausbeute zu 7-Methylpyrazolo[3,4-d]pyrimidin-4,6(5H)-dion (4).

     

New,convenient synthesis of 2-alkyl- and 2-vinylpyrazolo[3,4-d]-pyrimidine derivatives

Treatment of 1,3-dimethyl-6-hydrazinouracil with the appropriate dimethylformamide dialkylacetal afforded the, corresponding 2-alkyl-5,7-dimethylpyrazolo[3,4-d]pyrimidine-4,6-(5H,7H)diones. The reaction of 1,3-dimethyl-6-(α-methylbenzylidenehydrazino)uracils with dimethylformamide dimethylacetal or triethyl orthoformate gave the corresponding 5,7-dimethyl-2-vinylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)diones, respectively. Similarly, treatment of 1,3-dimethyl-6-(α-methylbenzylidenehydrazino)uraeils with triethyl orthopropionate yielded the corresponding 5,7-dimethyl-3-ethyl-2-vinylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)diones.     

Synthesis of 4,6-disubstituted-7-β-D-ribofuranosyl- and arabinofuranosylpyrazolo[3,4-d]pyrimidines and certain related ribonucleosides

Several disubstituted pyrazolo[3,4-d]pyrimidine, pyrazolo[1,5-a]pyrimidine and thiazolo[4,5-d]pyrimidine ribonucleosides have been prepared as congeners of uridine and cytidine. Glycosylation of the trimethylsilyl (TMS) derivative of pyrazolo[3,4-d]pyrimidine-4,6(1H,5H,7H)-dione ( 4 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose ( 5 ) in the presence of TMS triflate afforded 7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrazolo-[3,4-d]pyrimidine-4,6(1H,5H)-dione ( 6 ). Debenzoylation of 6 gave the uridine analog 7-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-4,6(1H,5H)-dione ( 3 ), identical with 7-ribofuranosyloxoallopurinol reported earlier. Thiation of 6 gave 7 , which on debenzoylation afforded 7-β-D-ribofuranosyl-6-oxopyrazolo[3,4-d]pyrimidine-4(1H,5H)-thione ( 8 ). Ammonolysis of 7 at elevated temperature gave a low yield of the cytidine analog 4-amino-7-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-6(1H)-one ( 11 ). Chlorination of 6 , followed by ammonolysis, furnished an alternate route to 11 . A similar glycosylation of TMS-4 with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride ( 12 ) gave mainly the N7-glycosylated product 13 , which on debenzylation provided 7-β-D-arabinofuranosylpyrazolo[3,4-d]pyrimidine-4,6(1H,5H)-dione ( 14 ). 4-Amino-7-β-D-arabinofuranosyl-pyrazolo[3,4-d]pyrimidin-6(1H)-one ( 19 ) was prepared from 13 via the C4-pyridinium chloride intermediate 17 . Condensation of the TMS derivatives of 7-hydroxy- ( 20 ) or 7-aminopyrazolo[1,5-a]pyrimidin-5(4H)-one ( 23 ) with 5 in the presence of TMS triflate gave the corresponding blocked nucleosides 21 and 24 , respectively, which on deprotection afforded 7-hydroxy- 22 and 7-amino-4-β-D-ribofuranosylpyrazolo[1,5-a]pyrimidin-5-one ( 25 ), respectively. Similarly, starting either from 2-chloro ( 26 ) or 2-aminothiazolo[4,5-d]pyrimidine-5,7-(4H,6H)-dione ( 29 ), 2-amino-4-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine-5,7(6H)-dione ( 28 ) has been prepared. The structure of 25 was confirmed by single crystal X-ray diffraction studies.     

Synthesis of 5′-amino- and 5′-azido-2′,5′-dideoxy nucleosides from thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Summary Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (4) was silylated and condensed with methyl 5-azido-2,5-dideoxy-3-O-(4-methylbenzoyl)-D-erythro-pentofuranoside (2) in the presence ofTMS triflate to afford the corresponding protected nucleoside6 and acyclic nucleoside7. Deprotection of6 with MeONa/MeOH at room temperature gave 1-(5-azido-2,5-dideoxy--D-erythro-pentofuranosyl)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (8) and the corresponding anomer9, whereas compound7 yielded 5-azido-2,5-dideoxy-1-(2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-1-yl)-1-O-methyl-D-erythro-pentitol (10) under the same reaction conditions. 1-(5-Amino-2,5-dideoxy--D-erythro-pentofuranosyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (11) was obtained on treating9 with Ph₃P in pyridine followed by hyrolysis with NH₄OH. The anomeric nucleosides14 and15 and the corresponding acyclic nucleoside16 were obtained when4 was trimethylsilylated and condensed with methyl 2-deoxy-3,5-di-O-(4-methylbenzoyl)-D-erythro-pentofuranoside (3) followed by deprotection with MeONa in MeOH. Compounds8 and9 were also obtained when the anomeric mixture14/15 was treated with a mixture of NaN₃, Ph₃P, and CBr₄ in dryDMF at room temperature.On leave from Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt     

Syntheses and Antimicrobial Activity of Some Novel 6‐Substituted Dibenzo[d,f][1,3,2]dioxaphophepin‐6‐oxides,Sulfides, and Selenides

6‐Substituted‐dibenzo[d, f][1,3,2]dioxaposphepin‐6‐oxides, sulfides, and selenides (5a–i, 6a–d, and 7a–d) were synthesized by reacting 2,2′‐biphenol (1) with phosphorus tribromide in the presence of triethylamine at 0–30°C and subsequent reaction of the monobromide (2) with different Grignard reagents (3) at room temperature. The products (4) were converted to corresponding oxides, sulfides, and selenides (5a–i, 6a–d, and 7a–d) by oxidation with H₂O₂ at room temperature and refluxing with sulfur and selenium respectively. The chemical structures of all the products were confirmed by analytical, IR, NMR (¹H, ¹³C, and ³¹P), and mass spectral data. Most of these compounds exhibited moderate antimicrobial activity.     

Synthesis of 5,7-disubstituted-4-β-D-ribofuranosylpyrazolo[4,3-d]-pyrimidines and 2,4-disubstituted-1-β-D-ribofuranosylpyrrolo[3,2-d]-pyrimidines as congeners of uridine and cytidine

The synthesis of the congeners of uridine and cytidine in the pyrazolo[4,3-d]pyrimidine and pyrrolo[3,2-d]-pyrimidine ring system is described. Glycosylation of the trimethylsilyl (TMS) derivative of pyrazolo[4,3-d)pyrimidine-5,7(1H,4H,6H)-dione (4) with either 1-bromo- or 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose 5 and 6 , respectively in the presence of a Lewis acid catalyst gave the protected nucleoside 7 , which on debenzoylation afforded the uridine analogue 4-β-D-ribofuranosylpyrazolo[4,3-d]pyrimidine-5,7(1H,6H)-dione (8). Thiation of 7 gave 13 , which on deprotection yielded 4-β-D-ribofuranosyl-5-oxopyrazolo[4,3-d]pyrimidine-7(1H,-6H)-thione (14). Ammonolysis of 13 gave a low yield of the cytidine analogue 15. A chlorination of 7 , followed by amination furnished an alternative route to 15. A similar glycosylation of TMS-4 with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride (16) gave mainly the N4 glycosylated product 17 , which on debenzylation furnished 4-β-D-arabinofuranosylpyrazolo[4,3-d]pyrimidine-5,7(1H,6H)-dione (18). 7-Amino-4-β-D-arabinofuranosylpyrazolo[4,3-d]pyrimidin-5(1H)-one (23) was prepared from 17 via the pyridinium chloride intermediate 21. Condensation of the TMS derivative of pyrrolo[3,2-d]pyrimidine-2,4(1H,3H,5H)-dione (24) with 6 , followed by deprotection of the reaction product gave 1-β-D-ribofuranosylpyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (26). Similarly, TMS-24 was reacted with 16 to give a mixture of the blocked nucleosides 31 and 32 , which on debenzylation afforded a mixture of two isomeric compounds 34 and 35. 1-β-D-Arabinofuranosylpyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (34) was converted to the ara-C analogue 38 via the 3-nitrotriazolyl intermediate 36. The structure of 38 was confirmed by single crystal X-ray diffraction studies.     

Synthesis and Characterization of Novel Chiral (1R,2R)-1,2-Bis[5-(Aminomethylphospinic Acid)-1,3,4-Thiadiazol-2-YL]Ethane-1,2-Diols

Abstract

(1R,2R)-1,2-bis[5-(arylideneamino)-1,3,4-thiadiazol-2-yl]ethane-1,2-diol (2a–d) were synthesized by using appropriate aldehydes and (1R,2R)-1,2-bis(5-amino-1,3,4-thiadiazol-2-yl)ethane-1,2-diol (1) as a starting compound. Then, the phosphinic acid component (3a–d) were obtained from (2a–d) and hypophosporus acid. In addition, the structures of the novel chiral compounds (2a–d) and (3a–d) were confirmed by elemental analyses, IR, ¹H-NMR, ¹³C-NMR, and ³¹P-NMR spectra.

¹H NMR and ¹³C NMR spectra for 1, 2a, and 3a (Figures S1–S6) are available online in the Supplemental Materials.     

Succinct and Facile Synthesis of Innovative Thiopyrimidines With Antimicrobial and Antitubercular Investigation

Abstract

To develop a series of bioactive heterocycles in minimum number of steps, 3-methyl- 4-(substituted phenyl)-1-phenyl-4,8-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5,7 (1H,6H)-dithione 2(a–j), 4-(4-substituted phenyl)-5-imino-3-methyl-1,6-diphenyl-4,5,6,8-tetrahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-7(1H)-thione 3(a–j), and N-[4-(subs- tituted phenyl)-3-methyl-1-phenyl-7-thioxo-1,4,7,8-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5-yl]thiourea 4(a–j) have been synthesized from amino nitrile functionality 1(a–j). The structures of the compounds were elucidated by IR, ¹H NMR, elemental analysis, and some representative ¹³C NMR and mass spectra. All the title compounds were screened for antimicrobial and antitubercular activities, while some representative compounds were tested for antioxidant activity. Out of synthesized compounds, compounds 1j (4-CH₃), 2d (4-F), 4c (4-OH), and 4i (3-Br) exhibited maximum inhibition against Mycobacterium Tuberculosis H₃₇Rv. Compound 3c (4-OH) revealed elevated efficacy against all tested bacterial strain, while compounds 1i (3-Br), 2c (4-OH), and 3h (3-NO₂) were found efficacious against Candida albicans as compared to standard drugs.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

SYNTHESIS AND CHEMISTRY OF SOME NEW 2-MERCAPTOIMIDAZOLE DERIVATIVES OF POSSIBLE ANTIMICROBIAL ACTIVITY

4,5-Diaryl-2,3-dihydro-2-mercaptoimidazoles (2a–e) were synthesized. They reacted with chloroacetic acid in gl. acetic acid/Ac ₂ O in presence of anhyd. sodium acetate afforded 5,6-diaryl-2,3-dihydro-imidazo[2,1-b]thiazol-3-ones (3a–d). Also these compounds were prepared by the action of chloroacetyl chloride on compounds (2) in pyridine. Compounds (3a–d) on condensation with aromatic aldehydes yield 2-arylmethylene-5,6-diaryl-2,3-dihydroimidazo[2,1-b]-thiazol-3-ones (4a–q). The latter compounds were prepared directly by the reaction of (2) with chloroacetic acid and the aromatic aldehydes. Compounds (3a–d) coupled with aryldiazonium salts in pyridine to give 2-arylhydrazono-5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazol-3-ones (5a–r). Also compounds (2) when reacted with 2 or 3-bromopropionic acid afford 2,3-di-hydro-5,6-diaryl-2-methylimidazo[2,1-b]thiazol-3-ones (6a–d) and 2,3-di-hydro-6,7-diaryl imidazo-[2,1-b]-1,3-thiazin-4-ones (7a–d), respectively. Compounds (3, 6, and 7) have been cleaved by aromatic amines to give the corresponding 2-(4′,5′-diaryl-2′,3′-dihydroimidazol-2′-yl)thioacetanilide (8a–f), 2-(2′,3′-dihydro-4′,5′-diaryl imidazol-2′-yl)thiopropionamide (9a–c), and 3-(2′,3′-dihydro-4′,5′-diaryl-imidazol-2′-yl)thiopropionamide (10a–d) respectively. All the prepared compounds show considerable antimicrobial activity against bacteria, yeast, and fungi.     

A Convenient Route to 1,3,4-Thiadiazoles,Thiazolidinone, Thiazoles,Pyridones, Coumarins,Triazolo[5,1-c]triazines,and Pyrazolo[5,1-c]triazines Incorporating Pyrazolone Moiety and Their Use as Antimicrobial Agents

Condensation of 4-acetyl-5-methyl-2-phenyl-2,4-dihydropyrazol-3-one (1) with hydrazine derivatives (2a–d) afforded hydrazone derivatives (3a–d), which reacted with alkyl halides 4a–c to give bis(alkylthio)methylene derivatives (5a–e). Also, 3a,b reacted with hydrazonyl halides 6a–d to give 1,3,4-thiadiazole (7a–d). Cyclization of 3c with ethyl bromoacetate and haloketones gave thiazolidinone and thiazole derivatives (8, 10a,b) respectively. Treatment of hydrazone (3d) with benzylidine malononitrile 13a,b gave pyridine (14a,b). In addition, cyclocondensation of 3d with phenolic aldehydes furnished coumarin derivatives (16a–c). Coupling of 3d with heterocyclic diazonium salts gave triazol[5,1-c]triazine (20) and pyrazolo[5,1-c]triazine (22). Some of the prepared products showed potent antimicrobial activity.     

Thiazolo[4,5-d]pyrimidines. Part I. synthesis and anti-human cytomegalovirus (HCMV) activity in vitro of certain alkyl derivatives

Alkyl derivatives of the thiazolo[4,5-d]pyrimidine congeners of guanine and uracil were prepared and assessed for in vitro activity against human cytomegalovirus (HCMV). The finding that the 3-pentyl 1b and 3-hexyl 1c derivatives of 5-aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione (1e) had potent in vitro anti-HCMV activity prompted a broader study of alkyl derivatives in this ring system. A series of 3-alkyl derivatives of 1e , viz. 1f-w , were prepared by direct alkylation of the sodium salt of 1e and by subsequent modifications, 2a-d. For comparison with 1c , 5-amino-2-hexylaminothiazolo[4,5-d]pyrimidin-7(6H)-one (4) was prepared and studied. The 3-(2-alkenyl) derivatives of 1e were found to be the more active antiviral agents with the Z isomer of 5-amino-3-(2-penten-1-yl)thiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione (1f) having the better therapeutic index. Analogous 4-(2-alkenyl) derivatives of 2-aminothiazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione 6a and 6b were also prepared but were found to have poor therapeutic indices. Single crystal X-ray diffraction analysis was used to unequivocally establish the structure of 1f.     

Synthesis of Benz[d]oxazolones Involving Concomitant Acetyl Migration from Oxygen to Nitrogen

Heating of o-acetoxybenzoyl azides 6–10 in toluene leads to the Curtius reaction, which, when followed by closure of oxazolone ring with concomitant migration of acetyl group from oxygen to nitrogen, produces 3-acetoxybenz[d]oxazol-2(3H)-ones 11–15, which undergo hydrolysis with hot dilute hydrochloric acid to furnish benz[d]oxazol-2(3H)-ones 17–21. Thermal reaction of 2-hydroxy-5-nitrobenzoyl azide (22) in toluene finally yields a mixture of 5-nitrobenz[d]oxazol-2(3H)-one (20) and 5-nitrobenz[d]isoxazol-3(2H)-one (23).     

Efficient Synthesis of N‐Oxide Derivatives: Substituted 2‐(2‐(Pyridyl‐N‐oxide)methylsulphinyl)benzimidazoles

Different substituted 2‐chloromethylpyridyl derivatives (6a–d) were oxidized with mCPBA to give the respective 2‐chloromethylpyridine‐N‐oxide derivatives (7a–d) at low temperature, which on condensation with 2‐mercapto‐1H‐benzimidazole (8a–c) in the presence of aprotic solvents give the 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfanyl]‐1H‐benzimidazole (9a–d) in good yield. Finally, 9a–d oxidized with mCPBA in chlorinated solvent gives a mixture of 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfonyl]‐1H‐benzimidazole (3a–d, 10%) and 2‐[[(pyridin‐2‐yl‐1‐oxide) methyl]sulfinyl]‐1H‐benzimidazole (4a–d, 90%) derivatives.     

Efficient Synthesis of New Pyrimido[5′,4′:5,6]pyrano[2,3-d]pyrimidine-2,4,6(1H,3H)-triones via the Tandem Intramolecular Pinner–Dimroth Rearrangement,and Their Antibacterial Activity

Synthesis of new 8-alkyl-5-aryl-1,3-dimethyl-5,7-dihydro-2H-pyrimido[5′,4′:5,6]pyrano[2,3-d]- pyrimidine-2,4,6(1H,3H)-triones by the high yield reaction of 7-amino-5-aryl-1,3-dimethyl-2,4-dioxo-1,3,4,5- tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitriles with aliphatic carboxylic acids in the presence of POCl3 is presented. It is probable that synthesis of these new products proceeds via the tandem intramolecular Pinner–Dimroth rearrangement. The products are characterized by FT-IR, ¹H, and ¹³C NMR spectra and evaluated for their antibacterial activity against gram +ve bacteria (Staphylococcus aureus and Staphylococcus epidermidis) and gram–ve bacteria (Escherichia coli and Pseudomonas aeruginosa) using the disc diffusion method.

     

A Facile Synthesis of New 3-Substituted-2,3- dihydropyrido[3,2-d]pyrimidine-2,4-diones

Abstract

Pyrido[3,2-d]pyrimidine-2,4-diones derivatives have been synthesized in good yields by two efficient synthetic routes, the first one through an hetero-cyclization on the ureas derivatives 3a–e under alkaline conditions, the second one by condensation of the isocyanate 2 with various arylalkylamines in pyridine.     

Synthesis and Antibacterial Activity of Substituted Thiosemicarbazides and of 1,3,4-Thiadiazole or 1,2,4-Triazole Derivatives

The synthesized series of new thiosemicarbazide derivatives ( 1 , 6–10 ) in reactions with carbon disulphide produced, according to the reaction conditions, the dithioacids ( 4 , 30 ) or the 5-substituted 1,3,4-thiadiazolo-2-thiol derivatives ( 2 , 27 ). The dithioacids were cyclized, in the reaction with hydrazine, into the 4-ami-no-1,2,4-triazolo-2-thiol derivatives ( 5 , 31 ). One of these compounds ( 31 ) was transformed into the 1,2,4-triazolo-1,3,4-thiadiazine derivative ( 33 ). The compo-unds 6–9 were also exposed to the condensation with aldehydes. 4-phenylpipera-zinocarbothiohydrazide ( 6 ) was exposed to the action of isothiocyanates, which gave the compounds 16–20 , and these cyclized to the 1,3,4-thiadiazoloamino derivatives ( 21–23 ).

The susceptibility of aerobic and anaerobic bacteria to some of the new derivatives were tested. The anaerobes were the most susceptible at concentrations in ranges less than 6.2 to 100 μg/mL to derivative: 9 (64% were susceptible), 1 , 13 (for 60%), and 7 (for 56%).     

Synthesis of certain pyrazolo[3,4-d]pyrimidin-3-one nucleosides

Synthesis of the pyrazolo[3,4-d]pyrimidin-3-one congeners of guanosine, adenosine and inosine is described. Glycosylation of 3-methoxy-6-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 13 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose ( 16 ) in the presence of boron trifluoride etherate gave 3-methoxy-6-methylthio-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 17 ) which, after successive treatments with 3-chloroperoxybenzoic acid and methanolic ammonia, afforded 6-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)one ( 18 ). The guanosine analog, 6-amino-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 21 ), was made by sodium iodide-chlorotrimethylsilane treatment of 6-amino-3-methoxy-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)one ( 19 ), followed by sugar deprotection. Treatment of the adenine analog, 4-amino-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one ( 11 ), according to the high temperature glycosylation procedure yielded a mixture of N-1 and N-2 ribosyl-attached isomers. Deprotection of the individual isomers afforded 4-amino-3-hydroxy-1-βribofuranosylpyrazolo-[3,4-d]pyrimidine ( 26 ) and 4-amino-2-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-3(7H)-one ( 27 ). The structures of 26 and 27 were established by single crystal X-ray diffraction analysis. The inosine analog, 1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 28 ), was synthesized enzymatically by direct ribosylation of 1H-pyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 8 ) with ribose-1-phosphate in the presence of purine nucleoside phosphorylase, and also by deamination of 26 with adenosine deaminase.     

Detailed studies on the reduction of aliphatic 3-, 4-, 6-, and 13-oximino esters: Synthesis of novel isomeric amino esters,oximino alcohols,and amino alcohols

The preparation of novel 3-, 4-, 6-, and 13-amino-tetradecanoic acid methyl esters (2a–d) obtained by the reduction of 3-, 4-, 6-, and 13-oximino-tetradecanoic acid methyl esters (1a–d), was investigated. Oximino esters were reduced to afford the corresponding amino esters using NaBH₄–ZrCl₄ reducing system with good yields (58–82%). However, the reduction of oximino esters with LiAlH₄ and BH₃. Tetrahydrofuran gave the corresponding novel 3-, 4-, 6-, and 13-oximino alcohols (3a–d), and 3-, 4-, 6-, and 13-amino alcohols (4a–d) respectively with good chemical yields.