Toward a general strategy for the synthesis of 3,4-dihydroxyprolines from pentose sugars.
A general strategy is proposed, wherein a pentose sugar gamma-lactone can be converted, via a series of nine reactions, to a 3,4-dihydroxyproline, suitably protected for use in peptide synthesis. Thus, D-ribonolactone (6) has been converted to N-fluorenylmethoxycarbonyl-3,4-di-O-tert-butyldimethylsilyloxy-D-2,3-cis-3,4-cis-proline (7) in 18.9% overall yield. Likewise, L-arabinonolactone (11) has been converted to N-fluorenylmethoxycarbonyl-3,4-di-O-tert-butyldimethylsilyloxy-L-2,3-cis-3,4-trans-proline (36) in 13.7% overall yield and L-lyxonolactone (12) to N-fluorenylmethoxycarbonyl-3,4-di-O-tert-butyldimethylsilyloxy-L-2,3-trans-3,4-cis-proline (37) in 11.2% overall yield. These building blocks have also been fully deprotected to give the free amino acids. We believe that this series of reactions ought to be applicable to the synthesis of any of the eight stereoisomers of 3,4-dihydroxyproline, by judicious selection of the pentose starting material.
Taylor
Carol M
CM
Institute of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand. C.M.Taylor@massey.ac.nz
Barker
William D
WD
Weir
Claudette A
CA
Park
Jae H
JH
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010429:Pentoses / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D010429:Pentoses; D011392:Proline