Synthesis of Acyclic Nucleotide Analogues Derived from 2-Amino-6-C-substituted Purines via Cross-Coupling Reactions of 2-Amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-halopurines with Diverse Organometallic Reagents

2000 ◽  
Vol 65 (8) ◽  
pp. 1357-1373 ◽  
Author(s):  
Michal Česnek ◽  
Michal Hocek ◽  
Antonín Holý
Keyword(s):  
Ion Exchange ◽  
Cross Coupling ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Nucleotide Analogues ◽  
Organometallic Reagents ◽  
Arylboronic Acids ◽  
Cross Coupling Reactions

Cross-coupling reactions of 2-amino-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}purine (1) and 2-amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-iodopurine (2) with diverse types of organometallic reagents have been studied. Arylboronic acids reacted with 1 to give the corresponding 2-amino-6-arylpurines 3a-3d in good yields. Analogously, trialkylaluminium reagents were used for the preparation of 6-alkyl-2-aminopurines 3k and 3l from 1. Hetarylzinc halides and hetarylstannanes required the use of 2-amino-6-iodopurine 2 to give the corresponding 2-amino-6-hetarylpurines 3e-3j in fair to good yields. A CuI/KF mediated coupling of perfluoroalkylsilanes with 2 afforded the 2-amino-6-perfluoroalkylpurines 3m and 3n in moderate yields. Cleavage of the esters 3 with bromo(trimethyl)silane gave the target free phosphonates 4 that were purified by ion- exchange chromatography. The title compounds were tested on antiviral and cytostatic activity.

Cytostatic 6-Arylpurine Nucleosides III. Synthesis and Structure-Activity Relationship Study in Cytostatic Activity of 6-Aryl-, 6-Hetaryl- and 6-Benzylpurine Ribonucleosides

2001 ◽  
Vol 66 (3) ◽  
pp. 483-499 ◽  
Author(s):  
Michal Hocek ◽  
Antonín Holý ◽  
Ivan Votruba ◽  
Hana Dvořáková
Keyword(s):  
Cross Coupling ◽  
Structure Activity Relationship ◽  
Cytostatic Activity ◽  
Activity Relationship ◽  
Coupling Reactions ◽  
Arylboronic Acids ◽  
Cross Coupling Reactions ◽  
Structure Activity ◽  
Relationship Study

A series of fifteen 6-aryl-, 6-hetaryl- and 6-benzylpurine ribonucleosides has been prepared by Pd-catalyzed cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)- purine with arylboronic acids, hetarylzinc halides, hetarylstannanes or benzylzinc halides followed by deprotection. Structure-activity relationship study revealed that besides 6-(4-substituted phenyl)purine nucleosides, also some 6-hetaryl- and 6-benzylpurine ribonucleosides possess considerable cytostatic activity.

Synthesis of Acyclic Nucleotide Analogues Derived from 6-Hetarylpurines via Cross-Coupling Reactions of 9-[2-(Diethoxyphosphonylmethoxy)ethyl]-6-iodopurine with Hetaryl Organometallic Reagents

1997 ◽  
Vol 62 (1) ◽  
pp. 136-146 ◽  
Author(s):  
Michal Hocek ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Cross Coupling ◽  
Coupling Reactions ◽  
Nucleotide Analogues ◽  
Organometallic Reagents ◽  
Cross Coupling Reactions ◽  
Adenine Derivative

The title acyclic nucleotide analogues derived from 6-hetarylpurines were prepared by Pd(0)-catalysed cross-coupling reactions of 9-[2-(diethoxyphosphonylmethoxy)ethyl]-6-iodopurine (1) with hetarylorganometallics: (pyridin-2-yl)-, (imidazol-2-yl)- and (pyrrol-2-yl)zinc chlorides or (imidazol-5-yl)- stannanes, followed by deprotection in fair to good yields. The starting 6-iodopurine derivative 1 was prepared by iododeamination of the adenine derivative.

Cytostatic 6-Arylpurine Nucleosides II. Synthesis of Sugar-Modified Derivatives: 9-(2-Deoxy-β-D-erythro-pentofuranosyl)-, 9-(5-Deoxy-β-D-ribofuranosyl)- and 9-(2,3-Dihydroxypropyl)-6-phenylpurines

2000 ◽  
Vol 65 (11) ◽  
pp. 1683-1697 ◽  
Author(s):  
Michal Hocek ◽  
Antonín Holý ◽  
Ivan Votruba ◽  
Hana Dvořáková
Keyword(s):  
Cross Coupling ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Cross Coupling Reactions ◽  
Highly Active ◽  
Phenylboronic Acids

9-(2-Deoxy-β-D-erythro-pentofuranosyl)-6-(4-substituted phenyl)purines, 9-(5-deoxy-β-D-ribofuranosyl)-6-(4-substituted phenyl)purines and 9-(2,3-dihydroxypropyl)-6-(4-substituted phenyl)purines were prepared by the Suzuki-Miyaura cross-coupling reactions of the corresponding protected 9-substituted 6-chloropurines with substituted phenylboronic acids followed by MeONa mediated deprotection. In contrast to the highly active 6-phenylpurine ribonucleosides, the title compounds did not show any considerable cytostatic activity.

Comparison of the Suzuki cross-coupling reactions of 4,7-dichloroquinoline and 7-chloro-4-iodoquinoline with arylboronic acids using phosphine-free palladium catalysis in water

2004 ◽  
Vol 82 (2) ◽  
pp. 206-214 ◽  
Author(s):  
Richard W Friesen ◽  
Laird A Trimble
Keyword(s):  
Phenylboronic Acid ◽  
Palladium Catalysis ◽  
Suzuki Reaction ◽  
Tetrabutylammonium Bromide ◽  
Cross Coupling ◽  
Palladium Acetate ◽  
Coupling Reactions ◽  
Reaction Conditions ◽  
Arylboronic Acids ◽  
Cross Coupling Reactions

4,7-Dichloroquinoline (1a) and 7-chloro-4-iodoquinoline (1b) undergo Suzuki cross-coupling reactions with arylboronic acids catalyzed by phosphine-free palladium acetate in boiling water. Using phenylboronic acid (2), the reaction of 1a provides 7-chloro-4-phenylquinoline (3) (78%) together with diphenylquinoline (4) (12%), while 1b reacts in a much more regioselective fashion and provides 3 in 98% isolated yield. Although 1b undergoes a more regioselective Suzuki reaction than 1a, additional important observations are that the overall reaction of 1b with 2 is three times slower than 1a and that the reaction occurs in the absence of tetrabutylammonium bromide. Using optimized reaction conditions, a variety of aryl and vinylboronic acids undergo regioselective Suzuki cross-coupling with 1b to provide the products 7, 10, and 11 in good to excellent yield.Key words: palladium, cross-coupling, regioselectivity, quinolines, boronic acids.

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