Shuto, Satoshi Shirato, Michiyo Sumita, Yuji Ueno, Yoshihito Matsuda, Akira Nucleosides and Nucleotides. 173. Synthesis of Cyclic IDP-carbocyclic-ribose, a Stable Mimic of Cyclic ADP-ribose. Significant Facilitation of the Intramolecular Condensation Reaction of <i>N</i>-1-(Carbocyclic-ribosyl)inosine 5‘,6‘‘-Diphosphate Derivatives by an 8-Bromo-Substitution at the Hypoxanthine Moiety Cyclic ADP-ribose (cADPR, <b>1</b>) is a general mediator involved in cellular Ca<sup>2+</sup> signaling. However, both the biological and chemical instability of cADPR limit studies on its physiological role. We designed cyclic ADP-carbocyclic-ribose (<b>3</b>) and its inosine congener <b>4</b> as stable mimics of cADPR and successfully synthesized <b>4</b>. Starting with cyclopentadiene, the optically active carbocyclic unit <b>8</b> was constructed via enzymatic optical resolution. S<sub>N</sub>2 reactions of <b>8</b> with inosine derivative <b>7</b> and the 8-bromoinosine derivative <b>25</b> gave the <i>N</i>-1-substituted derivatives <b>6</b> and <b>26</b>, which were converted to the corresponding diphosphate derivatives <b>5</b> and <b>22</b>. The intramolecular condensation reactions between the two phosphate groups of <b>5</b> and <b>22</b> were investigated. Although the reaction with inosine derivative <b>5</b> did not produce any of the cyclization product <b>20</b>, treatment of the corresponding 8-bromoinosine derivative <b>22</b> with EDC gave the desired intramolecular condensation product <b>29</b> in 23% yield. Thus, the significant effect of the 8-bromo group at the hypoxanthine moiety in facilitating the key intramolecular condensation reaction between the phosphate groups of the substrate <b>22</b> was recognized. This is possibly due to conformational restriction of the molecule in a syn-form around its glycosyl linkage. The 8-bromo and isopropylidene groups were removed in succession to give the target compound <b>4</b>. This is the first total synthesis of this type of cyclic nucleotide. intramolecular condensation reactions;diphosphate derivatives 5;S N 2 reactions;cADPR limit studies;target compound 4;intramolecular condensation reaction;carbocyclic unit 8;inosine congener 4;EDC;bromoinosine;cyclization product 20;Intramolecular Condensation Reaction;intramolecular condensation product 29;Cyclic;bromo;phosphate groups 1998-02-27
    https://acs.figshare.com/articles/journal_contribution/Nucleosides_and_Nucleotides_173_Synthesis_of_Cyclic_IDP-carbocyclic-ribose_a_Stable_Mimic_of_Cyclic_ADP-ribose_Significant_Facilitation_of_the_Intramolecular_Condensation_Reaction_of_i_N_i_-1-_Carbocyclic-ribosyl_inosine_5_6_-Diphosphate_Derivatives_by_an/3708501
10.1021/jo9717797.s001