Synthesis of 2-Substituted 6-(Hydroxymethyl)purine Bases and Nucleosides

2005 ◽  
Vol 70 (10) ◽  
pp. 1669-1695 ◽  
Author(s):  
Peter Šilhár ◽  
Radek Pohl ◽  
Ivan Votruba ◽  
Michal Hocek
Keyword(s):  
Adenosine Deaminase ◽  
Cross Coupling ◽  
The Other ◽  
Coupling Reactions ◽  
Purine Derivatives ◽  
Cytostatic Effect ◽  
Purine Bases ◽  
Cross Coupling Reactions ◽  
Zinc Iodide

A facile and efficient methodology of the synthesis of 6-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed based on Pd-catalyzed cross-coupling reactions of 6-halopurines or N-protected 2-amino-6-halopurines with (benzoyloxymethyl)zinc iodide followed by deprotection. Regioselective hydroxymethylations of 2,6-dihalopurines were also studied and used for the synthesis of 2-chloro-6-(hydroxymethyl)- or 2,6-bis(hydroxymethyl)purines. The 6-(hydroxymethyl)purine ribonucleoside 5f exerted high cytostatic effect and moderate inhibition of adenosine deaminase, while all the other derivatives were much less effective or entirely inactive.

Synthesis of 6-Amino-, 6-Methyl- and 6-Aryl-2-(hydroxymethyl)purine Bases and Nucleosides

2006 ◽  
Vol 71 (6) ◽  
pp. 788-803 ◽  
Author(s):  
Peter Šilhár ◽  
Radek Pohl ◽  
Ivan Votruba ◽  
Blanka Klepetářová ◽  
Michal Hocek
Keyword(s):  
Cross Coupling ◽  
Coupling Reactions ◽  
Purine Derivatives ◽  
Purine Bases ◽  
Arylboronic Acids ◽  
Cross Coupling Reactions ◽  
Zinc Iodide

An efficient methodology of the synthesis of 6-substituted 2-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed. Regioselective Pd-catalyzed cross-coupling reactions of 6-chloro-2-iodopurines with [(benzoyloxy)methyl]zinc iodide gave 2-[(benzoyloxy)-methyl]-6-chloropurines that were converted to 2-(hydroxymethyl)adenines by reactions with ammonia and to 6-methyl- or 6-aryl-2-(hydroxymethyl)purines by cross-coupling reactions with trimethylaluminium or arylboronic acids followed by deprotection. The title 6-substituted 2-(hydroxymethyl)purine bases and nucleosides did not exhibit significant cytostatic or anti-HCV activity.

scholarly journals Oxidative Photocatalytic Homo- and Cross-Coupling of Phenols: Non-Enzymatic, Catalytic Method for Coupling Tyrosine

2020 ◽  
Author(s):  
Kyle Niederer ◽  
Philip H. Gilmartin ◽  
Marisa Kozlowski
Keyword(s):  
High Selectivity ◽  
Cross Coupling ◽  
The Other ◽  
Nucleophilic Attack ◽  
Coupling Reactions ◽  
Catalytic Method ◽  
Cross Coupling Reactions ◽  
Oxidation Potentials ◽  
Coupling Partner ◽  
Radical Form

The first, oxidative photocatalytic method for phenol-phenol homo-coupling and cross-coupling is described and isolated yields of up to 97% are obtained. Measured oxidation potentials and computed nucleophilicity parameters are consistent with a nucleophilic attack of one partner onto the oxidized radical form of the other partner. Understanding of this model permitted development of cross-coupling reactions between nucleophilic phenols/arenes and easily oxidized phenols in high selectivity and efficiency. A highlight of this method is that one equivalent of each coupling partner is utilized. Building on these findings, the first non-enzymatic, catalytic method for coupling tyrosine was developed.

scholarly journals Oxidative Photocatalytic Homo- and Cross-Coupling of Phenols: Non-Enzymatic, Catalytic Method for Coupling Tyrosine

2020 ◽  
Author(s):  
Kyle Niederer ◽  
Philip H. Gilmartin ◽  
Marisa Kozlowski
Keyword(s):  
High Selectivity ◽  
Cross Coupling ◽  
The Other ◽  
Nucleophilic Attack ◽  
Coupling Reactions ◽  
Catalytic Method ◽  
Cross Coupling Reactions ◽  
Oxidation Potentials ◽  
Coupling Partner ◽  
Radical Form

The first, oxidative photocatalytic method for phenol-phenol homo-coupling and cross-coupling is described and isolated yields of up to 97% are obtained. Measured oxidation potentials and computed nucleophilicity parameters are consistent with a nucleophilic attack of one partner onto the oxidized radical form of the other partner. Understanding of this model permitted development of cross-coupling reactions between nucleophilic phenols/arenes and easily oxidized phenols in high selectivity and efficiency. A highlight of this method is that one equivalent of each coupling partner is utilized. Building on these findings, the first non-enzymatic, catalytic method for coupling tyrosine was developed.

New developments in direct functionalization of C–H and N–H bonds of purine bases via metal catalyzed cross-coupling reactions

RSC Advances ◽  
2015 ◽  
Vol 5 (55) ◽  
pp. 44371-44389 ◽  
Author(s):  
Morteza Abdoli ◽  
Zohreh Mirjafary ◽  
Hamid Saeidian ◽  
Ali Kakanejadifard
Keyword(s):  
Cross Coupling ◽  
Coupling Reactions ◽  
New Developments ◽  
Purine Bases ◽  
Cross Coupling Reactions ◽  
Concise Overview ◽  
Direct Functionalization ◽  
The Cross ◽  
Metal Catalyzed

This review provides a concise overview on the cross-coupling reactions in direct functionalization of purine bases in recent years.

scholarly journals Recent Applications of Pd-Catalyzed Suzuki-Miyaura and Buchwald-Hartwig Couplings in Pharmaceutical Process Chemistry.

2021 ◽  
Author(s):  
Balaram S. Takale ◽  
Fan Yi Kong ◽  
Ruchita R. Thakore
Keyword(s):  
Drug Development ◽  
Large Scale ◽  
Cross Coupling ◽  
The Other ◽  
Coupling Reactions ◽  
Complex Molecules ◽  
Pharmaceutical Ingredients ◽  
The Core ◽  
Cross Coupling Reactions ◽  
Process Chemistry

Cross coupling reactions have changed the way complex molecules are synthesized. In particular, Suzuki-Miyaura and Buchwald-Hartwig amination reactions have given opportunities to elegantly make pharmaceutical ingredients. Indeed, these reactions are forefront at both the stages of drug development, medicinal chemistry, and process chemistry. On one hand, these reactions have given medicinal chemists a tool to derivatize the core molecule to arrive at scaffold rapidly. On the other hand, these cross couplings have offered the process chemists a smart tool to synthesize the development candidates safely, quickly, and efficiently. Generally, the application of cross coupling reactions is broad, and this review will specifically focus on their real (pharma) world applications in large scale synthesis those appeared in last two years.

scholarly journals Synthesis of (purin-6-yl)acetates and their transformations to 6-(2-hydroxyethyl)- and 6-(carbamoylmethyl)purines

2009 ◽  
Vol 74 (7-8) ◽  
pp. 1035-1059 ◽  
Author(s):  
Zbyněk Hasník ◽  
Radek Pohl ◽  
Blanka Klepetářová ◽  
Michal Hocek
Keyword(s):  
Antiviral Activity ◽  
Cross Coupling ◽  
Significant Activity ◽  
Coupling Reactions ◽  
Nucleophilic Substitutions ◽  
Purine Bases ◽  
Cross Coupling Reactions ◽  
Novel Approach ◽  
Reformatsky Reagent ◽  
Activity Screening

A novel approach to the synthesis of (purin-6-yl)acetates was developed based on Pd-catalyzed cross-coupling reactions of 6-chloropurines with a Reformatsky reagent. Their reduction with NaBH4 and treatment with MnO2 gave 6-(2-hydroxyethyl)purines, while reactions with amines in presence of NaCN afforded 6-(carbamoylmethyl)purines. Mesylation of the 6-(2-hydroxyethyl)purines followed by nucleophilic substitutions gave rise to several 6-(2-substituted ethyl)purines. This methodology was successfully applied to the synthesis of substituted purine bases and nucleosides for cytostatic and antiviral activity screening. None of the compounds exerted significant activity.

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