Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 6;9(15):17368-17378.
doi: 10.1021/acsomega.4c00068. eCollection 2024 Apr 16.

Study of Direct N7 Regioselective tert-Alkylation of 6-Substituted Purines and Their Modification at Position C6 through O, S, N, and C Substituents

Filip Nevrlka  1 , Adam Bědroň  1 , Michal Valenta  1 , Lenka Tranová  1 , Jakub Stýskala  1
Affiliations

Study of Direct N7 Regioselective tert-Alkylation of 6-Substituted Purines and Their Modification at Position C6 through O, S, N, and C Substituents

Filip Nevrlka et al. ACS Omega. .

Abstract

A new N7 direct regioselective method allowing the introduction of tert-alkyl groups into appropriate 6-substituted purine derivatives is developed. This method is based on a reaction of N-trimethylsilylated purines with a tert-alkyl halide using SnCl4 as a catalyst. In this work, we study the structure and optimal reaction conditions leading to the N7 isomer and in some cases also to the N9 isomer. The main goal is devoted to preparing 7-(tert-butyl)-6-chloropurine as a suitable compound for other purine transformations. The stability of the tert-butyl group at the N7 position is tested for classic model reactions, leading to the preparation of new 6,7-disubstituted purine derivatives, which is also interesting from the point of view of possible biological activity.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Preparation of N7-Alkylated 6-Chloropurines
Scheme 2
Scheme 2. Preparation of N7/N9-(tert-Alkylated) Purine Derivatives
Figure 1
Figure 1
Resolution of N7/N9 regioisomers based on (a) chemical shift of the C5 carbon atom, determined using HMBC and HSQC experiments; (b) difference between the chemical shifts of the C5 and C8 carbon atoms; (c) NOESY NMR experiment.
Scheme 3
Scheme 3. Instability of the N7-(tert-Butyl) Group of 2 in the Presence of Acidic Compounds
Scheme 4
Scheme 4. Modification of 7-(tert-Butyl)-6-chloro-7H-purine (2) at Position C6
Scheme 5
Scheme 5. Illustration of the Problem of Substituting a Chlorine Atom with a Less Nucleophilic Amine
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. De Clercq E.; Li G. Approved Antiviral Drugs over the Past 50 Years. Clin. Microbiol. Rev. 2016, 29 (3), 695–747. 10.1128/CMR.00102-15. - DOI - PMC - PubMed
    1. Parker W. B. Enzymology of Purine and Pyrimidine Antimetabolites Used in the Treatment of Cancer. Chem. Rev. 2009, 109 (7), 2880–2893. 10.1021/cr900028p. - DOI - PMC - PubMed
    1. Duke C. C.; Liepa A. J.; MacLeod J. K.; Letham D. S.; Parker C. W. Synthesis of Raphanatin and Its 6-Benzylaminopurine Analogue. J. Chem. Soc. Chem. Commun. 1975, (24), 964.10.1039/c39750000964. - DOI
    1. Schwarz S.; Siewert B.; Csuk R.; Rauter A. P. New Antitumor 6-Chloropurine Nucleosides Inducing Apoptosis and G2/M Cell Cycle Arrest. Eur. J. Med. Chem. 2015, 90, 595–602. 10.1016/j.ejmech.2014.11.019. - DOI - PubMed
    1. Xavier N. M.; Goncalves-Pereira R.; Jorda R.; Hendrychová D.; Oliveira M. C. Novel Dodecyl-Containing Azido and Glucuronamide-Based Nucleosides Exhibiting Anticancer Potential. Pure Appl. Chem. 2019, 91 (7), 1085–1105. 10.1515/pac-2019-0106. - DOI

LinkOut - more resources