Synthesis of Ethyl (1S,2R,3S,4S,5S)-2,3-O-(Isopropylidene)-4-Hydroxy-Bicyclo[3.1.0]Hexane-Carboxylate from L-Ribose: A Versatile Chiral Synthon for Preparation of Adenosine and P2 Receptor Ligands.

Substitution of the ribose moiety of various nucleosides and nucleotides with the (N)-methanocarba ring system increases the potency and selectivity as ligands at certain subtypes of adenosine and P2 receptors. We have prepared a key intermediate in the synthesis of these derivatives, ethyl (1S,2R,3S,4S,5S)-2,3-O-(isopropylidene)-4-hydroxybicyclo[3.1.0]hexane-carboxylate (15), starting from L-ribose (8) as a readily available, enantiopure building block. L-ribose was converted to the corresponding 5'-iodo derivative (9), which was cleaved reductively with Zn. Improvements were made in subsequent steps corresponding to a published route to biologically important (N)-methanocarba 5'-uronamido nucleosides, and new steps were added to prepare related 5'-nucleotides.


Nucleosides Nucleotides Nucleic Acids. 2008;27(3):279-91

Joshi BV, Melman A, Mackman RL, Jacobson KA.
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.