39071-40-4Relevant academic research and scientific papers
Opened-ring adducts of 5-methylcytosine and 1,5-dimethylcytosine with amines and water and evidence for an opened-ring hydrate of 2′- deoxycytidine
Shetlar, Martin D.,Chung, Janet
, p. 818 - 832 (2011)
A variety of nucleic acid components and related compounds undergo photoreaction with water to form so-called photohydrates (e.g. uracil forms 6-hydroxy-5,6-dihydrouracil). However, the corresponding hydrates of 5-methylcytosine (a minor nucleobase in eukaryotic DNA) and related compounds have not been characterized. We report the preparation of opened-ring forms of such products for 5-methylcytosine (m5C) and 1,5-dimethylcytosine (DMC). This was accomplished via thermal reaction of ring-opened amine adducts (e.g. N-carbamoyl-3-amino-2-methylacrylamidine (IVa) or N-(N′-methylcarbamoyl)- 3-amino-2-methylacrylamidine (IVb)) produced by photo-induced reactions of m5C with ammonia or methylamine. When these adducts were treated with dilute trifluoroacetic acid, the amino group at the 3-position was replaced with a hydroxyl group; with IVa, N-carbamoyl-3-hydroxy-2-methylacrylamidine (Va) was formed, while reaction of IVb led to N-(N′-methylcarbamoyl)-3-hydroxy-2- methylacrylamidine (Vb). These compounds are ring-opened isomers of 5,6-dihydro-6-hydroxy-5-methylcytosine (Ia and IIa) and 5,6-dihydro-6-hydroxy-1, 5-dimethylcytosine (Ib and IIb). Compounds Va and Vb each undergo thermal ring closure reactions to form two unstable compounds with chemical and UV spectral properties expected for Ia and IIa (or Ib and IIb). The latter compounds have been identified as minor products in UV-irradiated aqueous solutions of m5C and DMC. Evidence is also presented that the 2′-deoxycytidine photohydrates coexist with an opened-ring form, possibly similar in nature to Vb. The nucleobase 5-methylcytosine (m5C) reacts photochemically with ammonia to form an opened-ring adduct (IVa); similar reactions occur with 1,5-dimethylcytosine and with methylamine. Subjection of such adducts to hydrolysis in dilute acid (e.g. 0.1% trifluoracetic acid) produces opened-ring hydrates of m5C (Va) and DMC. Photoreaction of the nucleoside 2′-deoxycytidine in water results in formation of closed-ring hydrates that equilibrate thermally with a compound that has the UV spectral properties expected for an adduct similar in nature to Va.
