Novel L-ribonucleotide (L-RNT) analogs were successfully synthesized utilizing the Mitsunobu reaction of L-ribonolactol (L-R) phosphonate derivatives with natural nucleic acid bases. The key intermediate, a vinyl diol phosphonate derivative, was prepared using cross metathesis (CM) as the core reaction from D-ribose. The protection of hydroxyl groups of D-ribose and the treatment of vinyl magnesium chloride provided a vinyl diol derivative, which was then reacted with diethyl vinyl phosphonate in the presence of a Hoveyda-Grubbs catalyst (II). Following this, the removal of the silyl group with TBAF and oxidation of a 1,2-diol group with NaIO<sub>4</sub> provided L-ribolactol (L-R) analogs in good yield. The Mitsunobu reaction of the lactol with the bases and the removal of acetonide group produced L-RNT phosphonates in good yield. Additionally, the CM reaction of vinyl diol derivatives with an excess of terminal olefin derivatives was successfully applied to prepare the corresponding vinyl diol analogs as precursors of L-ribonolactol analogs.

Efficient synthesis of L-ribonolactol derivative and their L-nucleoside analogs from D-ribose

2019 Fall National Meeting

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