A One-Pot Synthesis of Highly Functionalized Purines

Abstract

Highly substituted purines were synthesized in good to high yields through a one-pot straightforward metal-free scalable method, using the Traube synthesis adapted to Vilsmeier-type reagents. From 5-amino-4-chloropyrimidines, new 9-aryl-substituted chloropurines and intermediates for peptide nucleic acid synthesis were prepared. Variant procedures allowing a rapid synthesis of ribonucleosides and 7-benzylpurine from 5-amidino-6-aminopyrimidines are also reported to illustrate the high potential of this versatile toolbox. This route appears to be particularly interesting in the field of nucleic acids for a direct and rapid access to various new 8-alkylpurine nucleosides.

Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity

“…More recently, we developed a one-pot synthesis of highly functionalized purines from 4,6dichloropyrimidines allowing for example the rapid and efficient preparation of SBC001 in 86% yield [38][39][40].…”

Borane‐Catalyzed Hydrogenation of Tertiary Amides Activated by Oxalyl Chloride: DFT Mechanistic Insights

“…The doubly hydrogen‐bonded ion pair of C(NH 2 ) 3 + Cl – is 5.6 kcal/mol more stable than the solvated guanidinium and Cl – ions, suggesting even lower solubility in CHCl 3 solution. In contrast, the contact ion pairs of iminium chlorides such as 3 ‐Cl, a3 ‐Cl and 6 ‐Cl without strong H‐bonding are at least 8 kcal/mol Less stable than the separately solvated iminium and Cl – ions, strongly suggesting the freely solvated Cl – as the actual Lewis base for H 2 activation . Similarly, the contact ion pairs of quaternary ammonium halides [Me 4 N] + X – (X = Cl, Br and I) are also about 2.5 kcal/mol Less stable than the separated ions in solution.…”

“…More recently, mild one‐pot reduction of tertiary amides with H 2 is advanced by using oxalyl chloride (COCl) 2 as cleaner amide activation reagent and catalytic amount of borane BAr 3 (Ar = 2,6‐F 2 C 6 H 3 ) as Lewis acid catalyst, affording hydrochloride salts of tertiary amines that can be conveniently isolated by filtration. Experimentally, it is known that chlorination reagents such as (COCl) 2 and phosgene O=CCl 2 may react with the amide C=O group to form ionic chloroiminium chloride in solution, while the combination of borane BAr 3 and halides may act as frustrated Lewis pair (FLP) catalyst, for H 2 ‐cleavage. However, the detailed mechanism and energetics for the amide activation and reduction reactions, which is crucial for finding better catalysts and reaction conditions, still remains unclear and this will be the central topic of the present DFT study.…”

6‐Chloropurine Ribonucleosides from Chloropyrimidines: One‐Pot Synthesis

“…The development of a method to synthesize 6‐chloropurine ribonucleosides took place in efforts to obtain highly functionalized purines, especially 9‐aryl purines, in a one‐pot procedure (Décout et al., ; Zelli et al., ). For years, the purine scaffold has been used to develop both biological tools and bioactive compounds demonstrating the need for new easy ways to generate them (Rosemeyer, ).…”

“…However, such modifications allow access to new drug candidates or biological probes (Jao & Salic, ; Qu et al., ), demonstrating the crucial need for new methodologies to present easy paths to access these analogues. A straightforward method useful for the preparation of highly functionalized and easily modifiable purine nucleosides is described here (Décout, Zelli, Zeinyeh, Boucherle, & Haudecoeur, ; Zelli et al., ). The protocols describe the synthesis of several amidinoaminochloropyrimidines from commercially available dichloropyrimidines (Figs.…”