- An asymmetric synthesis of (-)-carbovir
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Enantioselective deprotonation of trans-4-t-butyldimethylsiloxymetyl-1,2-epoxycyclopentane (trans-4) by a chiral lithium amide, lithium (S)-2-(pyrrolidin-1-ylmethyl)pyrrolidide (1), afforded (1S,4S)-trans-4-t-butyldimethylsiloxymethyl-2-cyclopenten-1-ol (trans-7) in 83% ee. Alcohol trans-7 was easily transformed to (-)-carbovir, an anti-HIV carbocyclic nucleoside.
- Asami,Takahashi,Inoue
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Read Online
- ANTIVIRAL 4-(2-AMINO-6-HETEROCYLYL-9H-PURIN-9-YL)-2-CYCLOPENTENE-1 -METHANOL COMPOUNDS
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The present invention relates to certain antiviral compounds of formula I as defined herein that function as nucleoside reverse transcriptase inhibitors. The present invention also relates to processes for the preparation of these compounds, pharmaceutical compositions comprising them and to their use for the treatment of retroviral infections, and in particular their use in the treatment of HIV-1 virus.
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Paragraph 00117
(2017/02/28)
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- Novel salts of (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol
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The present invention relates to novel salts of (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1 -methanol of Formula I or solvates or hydrates thereof, wherein M represents hemimalonate, malonate, hemioxalate, oxalate, hydrobromide, dihydrobromide, hemimaleate, maleate.
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Page/Page column 10
(2011/04/25)
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- Enantioselective syntheses of carbanucleosides from the Pauson-Khand adduct of trimethylsilylacetylene and norbornadiene
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(Chemical Equation Presented) A new enantioselective approach to carbanucleosides from Pauson-Khand (PK) adduct 1 is disclosed. The chiral cyclopentenone 1 is readily accessible in enantiomerically pure form via PK reaction of trimethylsilylacetylene and norbornadiene using N-benzyl-N- diphenylphosphino-tert-butyl-sulfinamide as a chiral P,S ligand. (-)-Carbavir and (-)-Abacavir were enantioselectively synthesized starting from (-)-1. The key steps of the sequence are a photochemical conjugate addition of a hydroxymethyl radical, a retro-Diels-Alder reaction, and a palladium catalyzed allylic substitution to introduce the nucleobase.
- Vazquez-Romero, Ana,Rodriguez, Julia,Lledo, Agusti,Verdaguer, Xavier,Riera, Antoni
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supporting information; experimental part
p. 4509 - 4512
(2009/05/11)
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- PROCESS FOR THE PREPARATION OF (1S, 4R) -CIS-4-‘2-AMINO-6CHLORO-9H-PURIN-9-YL!-2-CYCLOPENTENE-1-METHANOL
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A process for preparing a chloropurine compound of formula (I) or a derivative thereof, which comprises ring closure of the compound of formula (VII) or a derivative thereof in the presence of catalytic acid and at least one equivalent of a formate derivative.
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Page/Page column 7-8
(2008/06/13)
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- Therapeutic nucleosides
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The present invention relates to intermediates useful for the preparation of certain compounds, for example, purine carbocyclic nucleosides.
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Page column 33-34
(2010/02/05)
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- Solid-phase synthesis of carbocyclic nucleosides.
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[formula: see text] An efficient solid-phase synthesis of carbocyclic nucleosides has been developed. The key step is the palladium-catalyzed coupling of a purine derivative to a resin-bound allylic benzoate. The resulting products may be further functionalized on the solid phase. Acidic cleavage affords carbocyclic nucleosides, a class of compounds with demonstrated biological activity and substantial current interest.
- Crimmins,Zuercher
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p. 1065 - 1067
(2007/10/03)
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- An efficient, general asymmetric synthesis of carbocyclic nucleosides: Application of an asymmetric aldol/ring-closing metathesis strategy
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A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.
- Crimmins,King,Zuercher,Choy
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p. 8499 - 8509
(2007/10/03)
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- Practical enantiodivergent syntheses of both enantiomers of carbovir, 1592U89 and six-membered ring analogues
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The hydroxylactones 4a-b (both available in optically pure form from biocatalytic processes) have been used in the preparation of carbovir, 1592U89, and their six-membered ring analogues.
- Olivo, Horacio F.,Yu, Jiaxin
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p. 391 - 392
(2007/10/03)
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- 6-deoxycarbovir: A xanthine oxidase activated prodrug of carbovir
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(-)-(cis)-4-(2-Amino-9H-purin-9-yl)-2-cyclopentenyl carbinol (6-deoxycarbovir) was prepared in order to evaluate prodrug approaches to increased bioavailability of the anti-HIV agent, (-)-carbovir. Incubation experiments demonstrated that 6-deoxycarbovir was rapidly converted to (-)-carbovir by the enzyme, xanthine oxidase. Since xanthine oxidase activity is present in both the intestine and liver, a high first pass conversion to carbovir would be expected in vivo.
- Vince,Brownell,Beers
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- A short synthesis of (-)-carbovir
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(-)-Carbovir ((-)-1) was synthesized via the cyclic carbonate 2 in four steps starting from enantiomerically enriched (-)-(s)-(cyclopent-2-enyl)methanol ((-)-3).
- Hildbrand,Troxler,Scheffold
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p. 1236 - 1240
(2007/10/02)
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- Potential Use of Carbocyclic Nucleosides for the Treatment of AIDS: Chemo-enzymatic Syntheses of the Enantiomers of Carbovir
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The lactam (1R,4S)-2-azabicyclohept-5-en-3-one , derived by whole cell enantiospecific hydrolysis of the racemate was converted into (-)-carbovir (-)-1 in ten steps.Lipase catalysed acetylation of 4-cis-hydroxycyclopent-2-enylmethyl tripheny
- Evans, Chris T.,Roberts, Stanley M.,Shoberu, Karoline A.,Sutherland, Alan G.
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p. 589 - 592
(2007/10/02)
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- Antiviral combination comprising nucleoside analogs
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Antiviral and antitumor compositions are disclosed comprising a mixture of AZT, ribavirin, d4T or CS-87 with a compound of general formula: STR1 wherein Z is H, OH or NH2, Y is CH, and X is selected from the group consisting of H, N(R)2, SR, OR or halogen, wherein R is H, lower(C1 -C4)alkyl, aryl or mixtures thereof, and the pharmaceutically-acceptable derivatives thereof.
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- 6-substituted purine carbocyclic nucleosides
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The present invention relates to 6-substituted purine carbocyclic nucleosides and their use in medical therapy particularly in the treatment of HIV and HBV infections. Also provided are pharmaceutical formulations and processes for the preparation of comp
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- Antiviral nucleoside combination
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Synergistic antiviral combinations of nucleoside derivatives; pharmaceutical formulations containing said combinations; use of the combinations in the treatment or prophylaxis of retroviral infections.
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- Guanine derivatives having antiviral activity and their pharmaceutically acceptable salts
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Amino acid esters of carbovir have been found to have improved bioavailability after oral administration compared with carbovir. The esters are particularly useful for the treatment of hepatitis B virus and retrovirus (e.g. human immunodeficiency virus) infections. A preferred amino acid ester is the valine ester.
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- Dideoxycarbocyclic nucleosides
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Antiviral and antitumor compounds are disclosed of general formula: STR1 wherein Z is H, OH or NH2, Y is CH or N, the bond indicated by C1 '--C2 ' is absent or, in combination with the C1 '--C2 ' bond is the unit CH=CH, and X is selected from the group consisting of H, N(R2), SR, OR or halogen, wherein R is H, lower (C1 -C4)alkyl, aryl or mixtures thereof, and the pharmaceutically acceptable salts thereof.
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- Optically-active isomers of dideoxycarbocyclic nucleosides
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Antiviral and antitumor compounds are disclosed of general formula: STR1 wherein Z is H, OR' or NH2, wherein R' is H, (C1 -C4)alkyl, aryl, CHO, (C1 -C16)alkanoyl or O=P(OH)2, Y is CH or N, and X is selected from the group consisting of H, N(R2), SR, OR' or halogen, wherein R is H, lower(C1 -C4)alkyl, aryl or mixtures thereof, and the pharmaceutically-acceptable salts thereof.
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- Optically-active isomers of dideoxycarbocyclic nucleosides
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Antiviral and antitumor compounds are disclosed of general formula: STR1 wherein Z is H, OR' or NH2, wherein R' is H, (C1 -C4)-alkyl, aryl, CHO, (C1 -C16)alkanoyl or O=P(OH)2, Y is CH or N, and X is selected from the group consisting of H, N(R2), SR, OR' or halogen, wherein R is H, lower-(C1 -C4)alkyl, aryl or mixtures thereof, and the pharmaceutically-acceptable salts thereof.
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