Stability and Reactivity of Cyclopentane Nucleoside Analogs in 98% w/w Sulfuric Acid

We synthesized seven carbocyclic nucleoside analogs featuring a cyclopentane ring in place of the (deoxy)ribose sugar, which serves as a linker in DNA/RNA nucleosides. We assessed the stability of cyclopentane nucleosides in 98% <i>w</i>/<i>w</i> sulfuric acid at room temperature via ¹H and ¹³C NMR spectroscopy. We observe that adenine (<b>A1</b>, <b>A4</b>), guanine (<b>G1</b>) and thymine (<b>T1</b>) cyclopentane nucleoside analogs remain stable for at least two weeks at room temperature, with only minor (~4%) degradation in <b>A1</b>. In contrast, the cytosine analog (<b>C1</b>) rapidly degrades to release a soluble cytosine. Methyl-substituted adenine analogs mimicking polymer backbone attachments at positions prone to tertiary carbocation formation (<b>A2</b>, <b>A3</b>) prove unstable and release soluble adenine. Only the 3,3-dimethylcyclopentyl adenine analog (<b>A4</b>) exhibits sufficient stability. Our findings reveal that cyclopentane serves as a viable stable linker in concentrated sulfuric acid for select nucleic acid bases, provided that the backbone connections avoid tertiary carbons susceptible to carbocation-mediated cleavage. We thus identify one potential key structural feature for engineering examples of genetic-like polymers that could potentially persist in Venus's concentrated sulfuric acid cloud environment.