1415645-50-9Relevant academic research and scientific papers
Synthesis of nucleobase-functionalized morpholino-modified nucleoside monomers through palladium-catalyzed cross-coupling reactions
Nandi, Bappaditya,Pattanayak, Sankha,Paul, Sibasish,Sinha, Surajit
, p. 1271 - 1286 (2013/04/10)
Morpholino-modified nucleoside analogues have widespread applications in developmental biology. To achieve nucleobase-functionalized forms of morpholino nucleosides, syntheses of 5-substituted cytidine, 8-substituted adenosine, and 8-substituted guanosine morpholino nucleoside monomers are described for the first time. The syntheses are based on the use of 5-iodocytidine, 8-bromoadenosine, and 8-bromoguanosine morpholino nucleosides as the key starting materials. These iodo or bromo derivatives have also been synthesized for the first time. Palladium-mediated cross-coupling reactions (Sonogashira, Suzuki, and Heck) were then employed with the halo derivatives to accomplish the substitutions. Different reaction conditions for C, A, and G were standardized to achieve the conversions. The strategy was devised in such a way that the useful N-trityl protecting groups remain at the end. The catalyst combinations used for Sonogashira, Suzuki, and Heck reactions were Pd(PPh3) 2Cl2·CuI, Pd(dppf)Cl2·CH 2Cl2, and Pd(OAc)2, respectively. Heck coupling between 5-iodocytidine monomer and methyl acrylate worked well, whereas with acrylonitrile the exocyclic amine of cytidine was found to form the aza-Michael adduct. In this context, treatment of iodocytidine with methyl acrylate under two different sets of conditions was found to produce either the Michael addition product or the Heck coupling product. Four of the functionalized morpholino monomers have been further confirmed by single-crystal X-ray structural analysis. All of these functionalized monomers were obtained in good to excellent overall yields. The synthesis of C-5-substituted cytidine and of C-8-substituted adenosine and guanosine morpholino nucleoside monomers by means of Pd-catalyzed cross-coupling (Sonogashira, Suzuki, and Heck) reactions is described. Various types of alkyne, aryl, and alkene group have been used to obtain diversely functionalized monomers from the corresponding iodo or bromo derivatives. Copyright
Improved protocol for the synthesis of flexibly protected morpholino monomers from unprotected ribonucleosides
Pattanayak, Sankha,Paul, Sibasish,Nandi, Bappaditya,Sinha, Surajit
, p. 763 - 782 (2013/01/16)
An inexpensive and much improved protocol has been developed for the synthesis of protected morpholino monomers from unprotected ribonucleosides in high overall yield, using oxidative glycol cleavage and reductive amination strategy. Unlike the previous methods, the present strategy allows installing the exocyclic amine protections at a later stage, and thus avoids the use of expensive, or commercially unavailable, exocyclic amine-protected ribonucleosides as starting materials. To demonstrate the flexibility of the present method in choosing protecting groups, the monomers have been protected with several such groups of different deblocking properties at the exocyclic amine position.
