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.

Synthesis of Novel Carbocyclic Nucleoside Analogues Derived from 2-(Hydroxymethyl)bicyclo[2.2.1]heptane

2007 ◽  
Vol 72 (11) ◽  
pp. 1523-1544 ◽  
Author(s):  
Milan Dejmek ◽  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Antonín Holý
Keyword(s):  
Mitsunobu Reaction ◽  
Nucleoside Analogues ◽  
Subsequent Reduction ◽  
Purine Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

The key intermediates, [(1R*,2R*,4R*,6R*)-6- (12a) and [(1R*,2R*,4R*,5S*)-5-(hydroxymethyl)- bicyclo[2.2.1]heptan-2-yl]methyl benzoates (12b), were prepared from (1R*,2S*,4R*)- bicyclo[2.2.1]hept-5-en-2-ylmethyl benzoate by hydroboration, oxidation with pyridinium dichromate and subsequent reduction of the thus obtained ketones. The Mitsunobu reaction of12aand12bwith 6-chloropurine afforded 6-chloropurine derivatives, which were converted into others purine analogues. Thymine analogues were prepared from [(1R*,2R*,4S*,6S*)-6- (25a) and [(1R*,2S*,4R*,5S*)-5-aminobicyclo[2.2.1]heptan-2-yl]methanols (25b), which were prepared from alcohols12aand12bin several easy steps.

New carbocyclic nucleoside analogues built on a bicyclo[2.2.2]octane-2,2-dimethanol template

2009 ◽  
Vol 74 (9) ◽  
pp. 1425-1441 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Antonín Holý
Keyword(s):  
Sulfonic Acid ◽  
Mitsunobu Reaction ◽  
Nucleoside Analogues ◽  
Hydroxy Derivative ◽  
Purine Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

(1R*,4S*,6S*)-6-(6-Chloro-9H-purin-9-yl)bicyclo[2.2.2]octane-2,2-dimethanol (22) and (1R*,4R*,5S*)-5-(6-chloro-9H-purin-9-yl)bicyclo[2.2.2]octane-2,2-dimethanol (17) were prepared from (1R*,4R*)-bicyclo[2.2.2]oct-5-ene-2,2-dimethanediyl dibenzoate (7) using two approaches. The first procedure consists in hydroboration of 7, separation of obtained 6-exo-hydroxy derivative 8 and 5-exo-hydroxy derivative 9, conversion of 8 and 9 to endo-hydroxy derivatives 12 and 13, respectively, and the Mitsunobu reaction with 6-chloropurine. Only 5-(6-chloropurinyl) analogue 16 was obtained in an acceptable yield. The target analog 17 was prepared by reductive debenzoylation of 16. The further reactions were hydroboration of 7, treatment with hydroxylamine-O-sulfonic acid and debenzoylation. Chloropurine analogues 17 and 22 were built on the obtained 6-exo-amino- and 5-exo-aminobicyclo[2.2.2]octane-2,2-dimethanols 18 and 19, respectively. Compounds 17 and 22 were converted to adenine (23, 24) and 6-(cyclopropylamino)purine analogues (25, 26).

Conformationally locked nucleoside analogues based on the bridgehead substituted 7-oxonorbornane and their antiviral properties

2011 ◽  
Vol 76 (12) ◽  
pp. 1549-1566 ◽  
Author(s):  
Milan Dejmek ◽  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Johan Neyts ◽  
Pieter Leyssen ◽  
...  
Keyword(s):  
Alder Reaction ◽  
Diels Alder ◽  
Nucleoside Analogues ◽  
Naphthalene Ring ◽  
Crucial Step ◽  
Diels Alder Reaction ◽  
Conformationally Locked

We report on the preparation of novel 1′-homonucleoside derivatives locked in a West conformation by 1′,4′-bridge consisting of annulated benzene or naphthalene ring. The crucial step of the synthesis was Diels–Alder reaction of an appropriate aryne with a suitable furane derivative. Antiviral properties of novel compounds were studied and slight activity against HCV was detected in several compounds.

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.

The Diels-Alder Reaction of 2-Ethenyl-1,4-Benzodioxin: A New and Simple Synthesis of Bisaryl Ethers

Synlett ◽  
1989 ◽  
Vol 1989 (01) ◽  
pp. 30-32
Author(s):  
Thomas V. Lee ◽  
Alistair J. Leigh ◽  
Christopher B. Chapleo
Keyword(s):  
Alder Reaction ◽  
Diels Alder ◽  
Simple Synthesis ◽  
Diels Alder Reaction

The intermolecular anthracene-transfer in a regiospecific antipodal C60 difunctionalization

2020 ◽  
Author(s):  
Radu Talmazan ◽  
Klaus R. Liedl ◽  
Bernhard Kräutler ◽  
Maren Podewitz
Keyword(s):  
Noncovalent Interactions ◽  
Interaction Model ◽  
Alder Reaction ◽  
Diels Alder ◽  
Stacking Interactions ◽  
Pi Stacking ◽  
Diels Alder Reaction ◽  
Double Decker ◽  
Anthracene Molecule ◽  
New Strategies

We analyze the mechanism of the topochemically controlled difunctionalization of C60 and anthracene, where an anthracene molecule is transferred from one C60 monoadduct to another one under exclusive formation of equal amounts of C60 and the difficult to make antipodal C60 bisadduct. Our herein disclosed dispersion corrected DFT studies show the anthracene transfer to take place in a synchronous retro Diels-Alder/Diels-Alder reaction: an anthracene molecule dissociates from one fullerene under formation of an intermediate, while already undergoing stabilizing interactions with both neighboring fullerenes, facilitating the reaction kinetically. In the intermediate, a planar anthracene molecule is sandwiched between two neighboring fullerenes and forms equally strong "double-decker" type pi-pi stacking interactions with both of these fullerenes. Analysis with the distorsion interaction model shows that the anthracene unit of the intermediate is almost planar with minimal distorsions. This analysis sheds light on the existence of noncovalent interactions engaging both faces of a planar polyunsaturated ring and two convex fullerene surfaces in an unprecedented 'inverted sandwich' structure. Hence, it sheds light on new strategies to design functional fullerene based materials.<br>

Natural Products Biosynthesis Involving a Putative Diels-Alder Reaction

2016 ◽  
Vol 20 (22) ◽  
pp. 2421-2442 ◽  
Author(s):  
Kévin Cottet ◽  
Maria Kolympadi ◽  
Dean Markovic ◽  
Marie-Christine Lallemand
Keyword(s):  
Natural Products ◽  
Alder Reaction ◽  
Diels Alder ◽  
Diels Alder Reaction
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