Synthesis of Novel Carbocyclic Nucleoside Analogues Containing Bicyclo[2.2.1]hept-2-ene-2-methanol

2008 ◽  
Vol 73 (1) ◽  
pp. 44-58 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Antonín Holý
Keyword(s):  
Acetic Acid ◽  
Hydrochloric Acid ◽  
Triethyl Orthoformate ◽  
Ring Closure ◽  
Methyl Benzoate ◽  
Nucleoside Analogues ◽  
Purine Derivatives ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

Starting ethyl (1R*,2R*,3R*,4S*)-3-bromobicyclo[2.2.1]hept-5-ene-2-carboxylate (9) was reduced with LiAlH4and benzoylated giving [(1R*,2R*,3R*,4S*)-3-bromobicyclo[2.2.1]hept-5-en-2-yl]methyl benzoate (11). Treatment of11with NaN3and CrO3in acetic acid afforded [(1R*,2S*,3R*,4R*,5S*,6R*)-6-azido-3-bromo-5-hydroxybicyclo[2.2.1]hept-2-yl]methyl benzoate (12a) and [(1R*,2S*,3S*,4R*,5S*,6R*)-5-azido-3-bromo-6-hydroxybicyclo[2.2.1]heptan-2-yl]-methyl benzoate (12b). These key intermediates were separated and converted in five reaction steps to (1R*,2R*,3S*,4S*)-3-[(5-amino-6-chloropyrimidin-4-yl)amino]-5-(hydroxymethyl)- bicyclo[2.2.1]hept-5-en-2-ol (17a) and (1R*,2R*,3S*,4S*)-3-[(5-amino-6-chloropyrimidin-4-yl)- amino]-6-(hydroxymethyl)bicyclo[2.2.1]hept-5-en-2-ol (17b). Ring closure with triethyl orthoformate led to (1R*,2R*,3S*,4S*)-5-(chloromethyl)-3-(6-chloro-9H-purin-9-yl)bicyclo[2.2.1]hept-5-en-2-ol (18a) and (1R*,2R*,3S*,4S*)-6-(chloromethyl)-3-(6-chloro-9H-purin-9-yl)- bicyclo[2.2.1]hept-5-en-2-ol (18b) using hydrochloric acid as a catalyst or (1R*,2R*,3S*,4S*)-3-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)bicyclo[2.2.1]hept-5-en-2-ol (19a) and (1R*,2R*,3S*,4S*)- 3-(6-chloro-9H-purin-9-yl)-6-(hydroxymethyl)bicyclo[2.2.1]hept-5-en-2-ol (19b) using trifluoro- acetic acid as a catalyst. From19aand19b, 6-amino- and 6-(cyclopropylamino)purine derivatives20and21were prepared.

Synthesis of novel carbocyclic nucleoside analogues derived from 7-oxabicyclo[2.2.1]heptane-2-methanol

2009 ◽  
Vol 74 (3) ◽  
pp. 487-502 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Armando M. De Palma ◽  
Johan Neyts ◽  
Antonín Holý
Keyword(s):  
Alder Reaction ◽  
Diels Alder ◽  
Methyl Benzoate ◽  
Mitsunobu Reaction ◽  
Nucleoside Analogues ◽  
Subsequent Reduction ◽  
Purine Analogues ◽  
Diels Alder Reaction ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

Hydroboration of [(1R*,2R*,4R*)-7-oxabicyclo[2.2.1]hept-5-en-2-yl]methyl benzoate (5), which was prepared by Diels–Alder reaction of furan with acrolein and subsequent reduction and benzoylation of the Diels–Alder product, afforded [(1R*,2S*,4S*,6S*)-6-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (6) and [(1R*,2R*,4R*,5S*)-5-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (7). The key intermediates, [(1R*,2S*,4S*,6R*)-6-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (10) and [(1R*,2R*,4R*,5R*)-5-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (11), were prepared from6and7, respectively, by oxidation with pyridinium dichromate and subsequent reduction of the thus obtained ketones. The Mitsunobu reaction of10and11with 6-chloropurine and subsequent reductive deprotection with diisobutylaluminium hydride afforded 6-chloropurine derivatives, which were converted to other purine analogues. Thymine analogues were prepared by Mitsunobu reaction of10and11with 3-benzoyl-5-methylpyrimidine-2,4(1H,3H)-dione and subsequent methanolysis. The target compounds were tested for the activity againstCoxsackievirus.

Synthesis of novel racemic carbocyclic nucleoside analogues derived from 4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol and 4-oxatricyclo[4.3.1.03,7]decane-10-methanol, compounds with activity against Coxsackie viruses

2009 ◽  
Vol 74 (3) ◽  
pp. 469-485 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Armando M. De Palma ◽  
Johan Neyts ◽  
Antonín Holý
Keyword(s):  
Alder Reaction ◽  
Diels Alder ◽  
Purine Nucleoside ◽  
Nucleoside Analogues ◽  
Lithium Aluminium Hydride ◽  
Subsequent Reduction ◽  
Lithium Aluminium ◽  
Diels Alder Reaction ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

(1R*,2R*,3R*,4S*)-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol (10) and (1R*,2R*,3R*,4S*)-bicyclo[2.2.2]oct-5-ene-2,3-dimethanol (14), which were prepared by the Diels–Alder reaction and subsequent reduction with lithium aluminium hydride, were treated with benzyl azidoformate to give benzylN-[(1R*,2R*,3S*,6S*,7S*,9S*)-9-(hydroxymethyl)-4,8-dioxatricyclo[4.2.1.03,7]nonan-2-yl]carbamate (11) and benzylN-[(1R*,2R*,3R*,6R*,7S*,10S*)-10-(hydroxymethyl)-4-oxatricyclo[4.3.1.03,7]decan-2-yl]carbamate (15). Hydrogenolysis of carbamates11or15afforded (1R*,2R*,3S*,6S*,7S*,9S*)-2-amino-4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol (12) or (1R*,2R*,3R*,6R*,7S*,10S*)-2-amino-4-oxatricyclo[4.3.1.03,7]decane-10-methanol (16). The amines12and16were transformed to thymine and purine nucleoside analogues. The target compounds were tested for the activity againstCoxsackievirus.

ChemInform Abstract: Unsaturated and Carbocyclic Nucleoside Analogues: Synthesis, Antitumor, and Antiviral Activity.

ChemInform ◽  
2010 ◽  
Vol 22 (24) ◽  
pp. no-no
Author(s):  
S. PHADTARE ◽  
D. KESSEL ◽  
T. H. CORBETT ◽  
H. E. RENIS ◽  
B. A. COURT ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

ChemInform Abstract: Asymmetric Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Potential Antiviral and Antitumor Agent

ChemInform ◽  
2008 ◽  
Vol 39 (11) ◽  
Author(s):  
Lak Shin Jeong ◽  
Jeong A. Lee ◽  
Hyung Ryong Moon ◽  
Hea Ok Kim ◽  
Kang Man Lee ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Antitumor Agent ◽  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

A Novel Approach to Khantiokerically Pure Carbocyclic Nucleoside Analogues

1987 ◽  
Vol 6 (1-2) ◽  
pp. 233-237 ◽  
Author(s):  
Michael Bodenteich ◽  
Kurt Faber ◽  
Gerhard Penn And ◽  
Herfried Griengl
Keyword(s):  
Nucleoside Analogues ◽  
Novel Approach ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

Asymmetric Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Potential Antiviral and Antitumor Agent

2007 ◽  
Vol 26 (6-7) ◽  
pp. 721-724 ◽  
Author(s):  
Lak Shin Jeong ◽  
Jeong A. Lee ◽  
Hyung Ryong Moon ◽  
Hea Ok Kim ◽  
Kang Man Lee ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Antitumor Agent ◽  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

ChemInform Abstract: An Efficient Organometallic Approach to New Carbocyclic Nucleoside Analogues.

ChemInform ◽  
2010 ◽  
Vol 33 (26) ◽  
pp. no-no
Author(s):  
Juraj Velcicky ◽  
Johann Lex ◽  
Hans-Guenther Schmalz
Keyword(s):  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues
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