Synthesis of (2R,3R,4S)-2-hydroxymethylpyrrolidine-3,4-diol from (2S)-3,4-dehydroproline derivatives.
(2R,3R,4S)-2-Hydroxymethylpyrrolidine-3,4-diol (1,4-dideoxy-1,4-imino-D-ribitol) was synthesized in five steps from N-protected (2S)-3,4-dehydroproline methyl esters. The stereoselective reaction of osmium tetraoxide with dehydroproline derivatives gave high yields of (2S,3R,4S)-3,4-dihydroxyprolines (2,3-trans-3,4-cis-3,4-dihydroxy-L-prolines) accompanied by small amounts (< 15%) of the diastereomeric (2S,3S,4R)-3,4-dihydroxyprolines (2,3-cis-3,4-cis-3,4-dihydroxy-L-prolines). The mixture of the diastereomeric glycols was converted into the isopropylidene acetals, and the isomers separated efficiently on a preparative scale. The resulting protected (2S,3R,4S)-3,4-dihydroxyproline methyl ester was reduced (LiBH4) to the 2-hydroxymethylpyrrolidine and deprotected, resulting in the production of (2R,3R,4S)-2-hydroxymethylpyrrolidine-3,4-diol in high yield and in high purity. The 1H and 13C NMR signals of the product have been unambiguously assigned using two-dimensional NMR techniques, and the identity of the title pyrrolidine confirmed by comparisons of its spectra with those reported for the authentic material.
Goli
D M
DM
Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, Cleveland 43606-3390.
Cheesman
B V
BV
Hassan
M E
ME
Lodaya
R
R
Slama
J T
JT
D000998:Antiviral Agents / Q000138:chemical synthesis*; D001089:Arabinose; D050113:Imino Furanoses; D009682:Magnetic Resonance Spectroscopy; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D013402:Sugar Alcohols / Q000138:chemical synthesis*
D000998:Antiviral Agents; D050113:Imino Furanoses; D013402:Sugar Alcohols; C058137:1,4-dideoxy-1,4-iminoarabinitol; C002195:3,4-dehydroproline; D011392:Proline; D001089:Arabinose