Green synthesis of nitroaryl thioureas: Towards an improved preparation of guanidinium DNA binders

Marco Minneci; Matas Misevicius; Isabel Rozas

doi:10.1016/j.bmcl.2023.129346

Green synthesis of nitroaryl thioureas: Towards an improved preparation of guanidinium DNA binders

Bioorg Med Chem Lett. 2023 Jun 15:90:129346. doi: 10.1016/j.bmcl.2023.129346. Epub 2023 May 20.

Authors

Marco Minneci¹, Matas Misevicius¹, Isabel Rozas²

Affiliations

¹ School of Chemistry, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
² School of Chemistry, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland. Electronic address: rozasi@tcd.ie.

PMID: 37217024
DOI: 10.1016/j.bmcl.2023.129346

Abstract

We present a general efficient green method for the preparation of nitro N,N'-diaryl thioureas via a one-pot method using cyrene as a solvent with almost quantitative yields. This confirmed the viability of cyrene as a green alternative to THF in the synthesis of thiourea derivatives. After screening different reducing conditions, the nitro N,N'-diaryl thioureas were selectively reduced using Zn dust in the presence of water and acid to the corresponding amino N,N'-diaryl thioureas. These were then used to test the installation of the Boc-protected guanidine group with N,N'-bis-Boc protected pyrazole-1-carboxamidine as a guanidylating reagent not requiring mercury(II) activation. Finally, the TFA salts obtained after Boc-deprotection of two sample compounds were tested for their affinity towards DNA showing no binding.

Keywords: Bis-Boc pyrazole-1-carboxamidine; Cyrene; Green solvent; Guanidylation; Nitro diaryl thioureas reduction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Guanidine
Guanidines*
Thiourea* / chemistry

Substances

Guanidine
Thiourea
Guanidines