An Improved Synthesis of S-3,4-Dehydroproline

S-3,4-dehydroproline ( 5 , S-Δ 3,4 -Pro) has been shown 1 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-Δ 3,4 -Pro has given analogues with modified biological activities. 2,3 In addition, reductive deuteration or tritiation of these S-Δ 3,4 -Pro containing peptides gives 3,4- 2 H 2 -Pro or 3,4- 3 H 2 -Pro analogues of high specific enrichment. 4 S-Δ 3,4 -Pro was initially obtained 5 by chemical resolution or selective enzymatic hydrolysis of R,S-3,4-dehydroprolinamide. A better process 4 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-Δ 3,4 -Pro ( 3 ) and the direct resolution of this material with natural (+)-tartaric acid. An important feature