Synthesis of Novel Racemic Conformationally Locked Carbocyclic Nucleosides Derived from 7-Substituted Bicyclo[2.2.1]hept-5-ene-2,2-dimethanols

2006 ◽  
Vol 71 (5) ◽  
pp. 635-649 ◽  
Author(s):  
Michal Šála ◽  
Hubert Hřebabecký ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Trifluoroacetic Acid ◽  
Palladium Catalyst ◽  
Carbocyclic Nucleosides ◽  
Purine Derivative ◽  
Adenine Derivative ◽  
Conformationally Locked

(1R*,4R*,7S*)-7-Aminobicyclo[2.2.1]hept-5-ene-2,2-dimethanol (15) was prepared in four easy steps from bicyclo[2.2.1]hept-5-ene-2,2-dimethanol (10). Reaction of amine 15 with ethyl N-((E)-3-ethoxymethacryloyl)carbamate afforded thymine derivatives 17a. The amine 15 was used to construct 6-chloro-9H-purine derivative 19a, 2-amino-6-chloro-9H-purine derivative 22a. Ammonolysis of 19a led to the adenine derivative 20a. Treatment of 22a with trifluoroacetic acid afforded guanine nucleoside 23a. (1R*,4R*,7S*)-7-[6-(Cyclopropylamino)-9H-purin-9-yl]bicyclo[2.2.1]hept-5-ene-2,2-dimethanol (21a) and (1R*,4R*,7S*)-7-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]bicyclo[2.2.1]hept-5-ene-2,2-dimethanol (24a) were prepared by aminolysis of 19a and 22a. Saturated nucleosides 17b, 20b, 21b, 23b, 24b were obtained by hydrogenation on palladium catalyst.

Synthesis of Novel Conformationally Locked Carbocyclic Nucleosides Derived from 3-(Hydroxymethyl)bicyclo[2.2.1]heptane-2,5-diol

2006 ◽  
Vol 71 (6) ◽  
pp. 871-888 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Milena Masojídková ◽  
Martin Dračínský ◽  
Antonín Holý
Keyword(s):  
Liquid Ammonia ◽  
Transfer Hydrogenation ◽  
Carbocyclic Nucleosides ◽  
Purine Analogues ◽  
Purine Derivative ◽  
Purine Analogue ◽  
Conformationally Locked

(1R*,2R*,3R*,4R*,5R*,6S*)-3-Amino-5-(benzyloxy)-6-(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (18) was prepared in seven easy steps from benzyl (1R*,2S*,3S*,4S*)-3-(benzyloxy)bicyclo[2.2.1]hept-5-ene-2-carboxylate (10). Reaction of amine18with ethylN-((2E)-3-ethoxymethacryloyl)carbamate afforded 1-[(1R*,2R*,3R*,4R*,5S*,6R*)-6-(benzyloxy)-3-hydroxy-5- (hydroxymethyl)bicyclo[2.2.1]heptan-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione (21) and after deprotection by transfer hydrogenation, free thymine analogue22. The thymine derivative21was converted to 2,3'-anhydronucleoside26. Treatment of the benzyl derivative18with sodium in liquid ammonia led to amine19, which was used as key intermediate for the construction of (1R*,2R*,3R*,4R*,5R*,6S*)-3-(6-chloro-9H-purin-9-yl)-6-(hydroxymethyl)-bicyclo[2.2.1]heptane-2,5-diol (28) and (1R*,2R*,3R*,4R*,5R*,6S*)-3-(2-amino-6-chloro-9H-purin-9-yl)-6-(hydroxymethyl)bicyclo[2.2.1]heptane-2,5-diol (33). Ammonolysis of28led to 6-amino-9H-purine derivative29. 6-(Dimethylamino)-9H-purine analogue30and 6-(cyclopropylamino)-9H-purine analogues31and34were prepared by aminolysis of corresponding chloropurine derivatives.

scholarly journals Contrasting Behavior of Conformationally Locked Carbocyclic Nucleosides of Adenosine and Cytidine as Substrates for Deaminases

2009 ◽  
Vol 28 (5-7) ◽  
pp. 614-632 ◽  
Author(s):  
Victor E. Marquez ◽  
Gottfried K. Schroeder ◽  
Olaf R. Ludek ◽  
Maqbool A. Siddiqui ◽  
Abdallah Ezzitouni ◽  
...  
Keyword(s):  
Carbocyclic Nucleosides ◽  
Conformationally Locked

Conformationally Locked Carbocyclic Nucleosides: Synthesis of the 1-Methyl-6-oxabicyclo[3.1.0]hexane Scaffold

Synlett ◽  
2006 ◽  
Vol 2006 (14) ◽  
pp. 2215-2218
Author(s):  
Gérard Audran ◽  
Honoré Monti ◽  
Yoann Aubin
Keyword(s):  
Carbocyclic Nucleosides ◽  
Conformationally Locked

Synthesis of Racemic 9-(6- and 2,6-Substituted 9H-Purin-9-yl)-5-oxatricyclo[4.2.1.03,7]nonane-3-methanols, Novel Conformationally Locked Carbocyclic Nucleosides

2005 ◽  
Vol 70 (1) ◽  
pp. 103-123 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Carbocyclic Nucleosides ◽  
Purine Derivatives ◽  
Purine Analogues ◽  
Derivatives Of ◽  
Conformationally Locked

(1R*,3R*,6R*,7S*,9S*)- and (1R*,3R*,6R*,7S*,9R*)-9-Amino-5-oxatricyclo[4.2.1.03,7]nonane-3-methanols (16aand17a) were prepared from 2-(hydroxymethyl)bicyclo[2.2.1]hept-5-ene-2-methanol (10) in five easy steps. The amines16aand17awere used to construct 6-chloro-9H-purine20and21, 2-amino-6-chloro-9H-purine30and31, and 6-chloro-8-methyl-9H-purine analogues34and35. Ammonolysis of these compounds led to 6-amino-9H-purine22aand23a, 2,6-diamino-9H-purine32and33, and 6-amino-8-methyl-9H-purine derivatives of 5-oxatricyclo[4.2.1.03,7]nonane-3-methanol36and37. (1R*,3R*,6R*,7S*,9S*)- and (1R*,3R*,6R*,7S*,9R*)-9-[6-(Dimethylamino)-9H-purin-9-yl]-5-oxatricyclo[4.2.1.03,7]nonane-3-methanols (22band23b), and (1R*,3R*,6R*,7S*,9S*)- and (1R*,3R*,6R*,7S*,9R*)-9-[6-(cyclopropylamino)-9H-purin-9-yl]-5-oxatricyclo[4.2.1.03,7]nonane-3-methanols (22cand23c) were prepared by aminolysis of20and21.

Synthesis of conformationally locked carbocyclic nucleosides with norbornane as pseudosugar moiety

2011 ◽  
Author(s):  
Milan Dejmek ◽  
Hubert Hřebabecký ◽  
Michal Šála ◽  
Martin Dračínský ◽  
Radim Nencka
Keyword(s):  
Carbocyclic Nucleosides ◽  
Conformationally Locked
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