Syntéza fosfonátových analog nukleotidů prolinolového typu

Vaněk, Václav

4. Conclusion A series ofnovel isosteric 3'-nucleotide analogues (9a-e and l0a-e) was synthesized, cr-t-- and B-t--prolinol nucleoside N-methylphosphonic acids distinguished for the loss of unambiguously defined configuration at the nitrogen atom in 3'-position of prolinol nng. Remarkable conformational differences between cr-L- and B-l-prolinol nucleotides determined by NMR study suggest some similarity with the natural 5'-o-nucleotide. The same conformational changes in o-series of prolinol nucleotides fit even better the 3'- and 5'-o- nucleotides. In addition, a series of four diastereoisomeric synthons 5-8 was prepared from the commercially available lrans-4-hydroxy-l-proline, giving access to a complete set of prolinol-derived nucleotide analogues bearing cr.L-, B-t--, o.o- and p-o-conÍiguration. In order to constrain the conformational flexibility of the N-phosphonomethyl moiety, seveÍal protected compounds were subjected to N-oxidation or N-methylation which gave chiral N-oxides or quatemary ammonium salts. However, the synthesis of the respective unprotected phosphonic acids was unsuccessful, probably due to their fast decomposition. Acylation ofthe pyrrolidine ring nitrogen atom by several acylphosphonic acid derivatives led to the novel N.phosphonoformyl, /y'.phosphonoacetyl and...

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