Carbocyclic Analogs of Nucleosides. Part 3. Synthesis of a new sulfone analog of cyclic adenosine 3′,5′‐monophosphate

Abstract

AbstractThe novel uncharged analog 2 of adenosine 3′,5′ ‐monophosphate (1) was prepared in its racemic form. To increase membrane permeability, the phosphate diester monoanion group of 1 was replaced by a dimethylene sulfone unit ( = methanosulfonylmethano group), and the 2′‐OH group was removed. To decrease lability against acid‐catalyzed depurination, the ring O‐atom was replaced by a CH2 group. All three modifications are also expected to increase the stability of analog 2 towards enzymatic degradation. The carbocyclic skeleton of 2 was constructed from trinorbornenecarbaldehyde 3 (see Scheme 1–3), and the adenine precursor 6‐chloropurine was introduced in the carbocyclic unit via an SN2 reaction based on Mitsunobu chemistry (Schemes 4 and 5).