An Improved Synthesis of S-3,4-Dehydroproline |
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Authors: | John W. Scott Antonio Focella Urs O. Hengartner David R. Parrish Donald Valentine Jr. |
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Affiliation: | Chemical Research Department , Hoffmann-La Roche Inc. , Nutley, New Jersey, 07110 |
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Abstract: | S-3,4-dehydroproline (5, S-Δ3,4-Pro) has been shown1 to be a potent inhibitor of collagen synthesis in mammalian cells due, at least in part, to its action as a prolyl hydroxylase inhibitor. The replacement in peptides of proline with S-Δ3,4-Pro has given analogues with modified biological activities.2,3 In addition, reductive deuteration or tritiation of these S-Δ3,4-Pro containing peptides gives 3,4-2H2-Pro or 3,4-3H2-Pro analogues of high specific enrichment.4 S-Δ3,4-Pro was initially obtained5 by chemical resolution or selective enzymatic hydrolysis of R,S-3,4-dehydroprolinamide. A better process4 involves resolution of R,S-N-t-butyloxycarbonyl-3,4-dehydroproline with R-α-methyl-p-nitrobenzylamine. In this paper, we report improvements in the synthesis of R,S-Δ3,4-Pro (3) and the direct resolution of this material with natural (+)-tartaric acid. An important feature |
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