Synthesis of Carbocyclic Homo-N-Nucleosides from Iridoids

Franzyk, Henrik; Rasmussen, Jon H.; Mazzei, Raffaele Antonio; Jensen, Søren Rosendal

doi:10.1002/(sici)1099-0690(199812)1998:12<2931::aid-ejoc2931>3.0.co;2-c

Cited by 18 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed instability of the triazine O -nucleoside analog 2 ( Scheme 1 ), prompted us to design the potentially more stable triazine homo- N -nucleoside analogs, 4 ( Figure 5 ). N -glycosidic nucleoside analogs represent a known, well established class of stable modified nucleosides [ 33 , 34 , 35 , 36 , 37 ]. For increased stability, the linking ether group was thus replaced by the corresponding –CH 2 -NH- linker.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

Schwidom

Exner

et al. 2008

Molecules

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

Schwidom

Exner

et al. 2008

Molecules

View full text Add to dashboard Cite

show abstract

“…Compound 17a was prepared by TBDMS-protection of diol 6, mesylation of the resulting compound 14, and replacement of the mesyl group of 15 with chloropurinyl in analogy to the preparation of 10 from 9. In view of the reported preparation of methylene-linked nucleoside analogues by reaction between the tetrabutylammonium salt of 6-chloropurine and a primary triflate, 12 we also tried to obtain 17a by generating the triflate of pseudosugar 14 (compound 18) and treating it with the Bu 4 N + salt in question, but the yield of 17a obtained by this method never exceeded 8%.…”

Section: Figurementioning

confidence: 99%

“…This concentrate was stirred with 4 Å molecular sieves (ca. 2.5 g) for 1 h at 0 ºC, and then treated with the tetrabutylammonium salt of 6-chloropurine (0.27 mg, 0.68 mmol), previously prepared from 6-chloropurine as described Franzyk et al 12 Stirring was continued for 64 h at -10 ºC, after which the mixture was filtered and the filtrate was concentrated to dryness, leaving a residue (0.57 g) that was fractionated on a silica gel column using hexane-EtOAc (1:1), hexane-EtOAc (1:3) and 2% MeOH-EtOAc as successive eluents. The middle fractions afforded 17a (27 mg, 8%) as a white solid with spectroscopic data identical to those of the compound obtained by Method A.…”

Section: Compound 17amentioning

confidence: 99%

A Convenient Synthesis of New Purinyl-homo-carbonucleosides on a Cyclopentane Ring Fused with Pyridazine

Caamaño¹,

Gómez²,

Fernández³

et al. 2004

Synthesis

View full text Add to dashboard Cite

The new purinyl homo-carbonucleosides 10 and 17a were prepared from 1,4-diphenyl-5,8-dihydro-5,8-methanophthalazine by one-pot ozonolysis and reductive cleavage, followed by monoprotection with an Ac or TBDMS group, mesylation of the resulting diol and replacement of the mesyl group with 6-chloropurine in the presence of NaH and 18-crown-6 ether. Homo-carbonucleosides 12 and 13 were then obtained from 10 by substitution of the chlorine in purine position 6. Compounds 17b and 19 were obtained from 17a in the same way.In keeping with the general antineoplastic and antileukemic properties of purine bases and their nucleosides, 1 natural and synthetic carbocyclic nucleosides can have significant antitumour and/or antiviral activity. 2 In particular, carbovir 3 (1) and abacavir 4 (2) have potent anti-HIV activity. In previous work, our research group synthesized several abacavir analogues with structures of type 3 (Figure 1), 5 some of which have shown marked cytostatic activity against human T lymphocytes (Molt4/C8 and CEM/0 cells). 6 Figure 1Most of these analogues have had an oxo or amino group at purine position 6 so as to maintain the ability of the natural nucleobase to form hydrogen bonds with polymerases and other key enzymes of nucleic acid metabolism. 7 In order to modify the lipophilicity and polar interactions of the pseudosugar moiety while retaining its rigidity, we have also begun to explore a class of analogues in which the benzene ring of 3 is replaced by an aromatic heterocycle. 8 Here we describe the synthesis of a number of compounds of this kind in which the heterocycle is pyridazine.The key intermediate 6 was prepared from 1,4-diphenyl-5,8-dihydro-5,8-methanophthalazine (4, obtained 9 from 2,3-dibenzoylbicyclo[2.2.1]hepta-2,5-diene). Initially, this was achieved by a method which parallels that previously employed 8b to prepare 1-and 2-alkyl derivatives of exo, exo-5,6-dihydroxy-4,5,6,7-tetrahydro-4,7-methanoindazoles. In this method (Method A), hydroxylation of the 'exposed' double bond of 4 was followed by oxidative cleavage of the resulting diol 5 (with sodium periodate and silica gel) 8,10 and reduction of the dialdehyde product by NaBH 4 in MeOH (Scheme 1). Subsequently, we discovered that 4 can be transformed cleanly into 6 in high yield (93%) in a one-pot process consisting of ozonolysis followed by reductive cleavage of the resulting ozonide (Method B).To monoprotect compound 6 in readiness for its coupling with the nucleobase, and in the light of previous experience, 5 we first attempted to acetylate it by enzymatic transesterification from vinyl acetate in dimethylformamide with Novozym ® 435 as catalyst. However, several attempts under various reaction conditions (temperatures of 20-50 °C and reaction times of 1-18 h) failed to provide acetylated products, so chemical acetylation was resorted to. Refluxing a 1:1.06:2.3 mixture of compound 6, acetic anhydride and pyridine in anhydrous THF for 8 hours afforded a 58% yield of 7 accompanied by a 32% yield of the diacetylate 8.Although Mi...

show abstract

“…In the series of 2′- or 3′-hydroxymetyl cyclopentane -1′-homocarbanucleosides, a few compounds presented a slight antiviral or anticancer activity [18,19], while 1′,3′-disubstituted cyclopentene analogs [20] or 2′,3′- cis diols [21], were found to be inactive. Other analogs synthesized had low or no antiviral activity [22,23,24], with the exception of the adenine analog [24]. However, a few chemical structures were fruitfully used to obtain active 1′-homocarbanucleosides (Figure 2), like for example: V , with a 2,2,3-trimethylcyclopentanol, active against HIV-1 and HIV-2 at an EC 50 = 4–14 µg/mL [25,26].…”

Section: Introductionmentioning

confidence: 99%

New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

Tănase

Drăghici²,

Hanganu³

et al. 2019

Molecules

View full text Add to dashboard Cite

New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (5) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (6j and 6d) had lower IC50 (15 ± 2 and 21 ± 4 µM) and compound 6f had an identical value of IC50 (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.

show abstract

Synthesis of Carbocyclic Homo-N-Nucleosides from Iridoids

Cited by 18 publications

References 21 publications

Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

A Convenient Synthesis of New Purinyl-homo-carbonucleosides on a Cyclopentane Ring Fused with Pyridazine

New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

Contact Info

Product

Resources

About