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.
Joshi
Bhalchandra V
BV
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-0810, USA.
Melman
Artem
A
Mackman
Richard L
RL
Jacobson
Kenneth A
KA
D000241:Adenosine / Q000737:chemistry* / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012266:Ribose / Q000737:chemistry*; D013237:Stereoisomerism
D006575:Heterocyclic Compounds, 3-Ring; D008024:Ligands; D009705:Nucleosides; D009711:Nucleotides; D018048:Receptors, Purinergic P2; C528914:ethyl 2,3-O-isopropylidene-4-hydroxybicylco(3.1.0)hexanecarboxylate; D012266:Ribose; D000243:Adenosine Deaminase; D000241:Adenosine