(2'S, 3S/R)-4-(N-tert-Butoxycarbonylpyrrolidin-2-yl)-4-oxo-3-phenylsulfonyl butanoyl-glycylglycine methyl ester (12) (2.42g, 5.02mmol) was dissolved in methanol (30ml), and the solution cooled to -10degC under argon. Sodium borohydride (188mg, 4.97mmol) was added and the mixture stirred at -10degC under argon until tlc analysis indicated complete consumption of the sulfone (ca. 10min.). Next, anhydrous disodium hydrogenphosphate (8.19g, 57.72mmol) was added, followed immediately by 5% sodium amalgam (22.43g, 48.77mmol). The mixture was allowed to warm to room temperature, stirred for 5h, then 1M hydrochloric acid (100ml) was added. The solution was decanted away from the mercury precipitate, diluted with water (100ml), and then extracted with ethyl acetate (3x100ml). The combined extracts were washed with saturated sodium hydrocarbonate (100ml), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate 1:1) to give (2'S, 3E)-4-(N-tert-butoxycarbonylpyrrolidin-2-yl)but-3-enoylglycylglycine methyl ester (19) (0.33g, 21%) as a colourless oil, [alpha]D -8deg (c 1.0, dichloromethane).

Proton Nmr deltaH (300MHz, CDCl3) 1.38(9H, s, OC(CH3)3), 2.06-1.65(4H, m, 2xCH2), 2.99(2H, apparent d, J=6.0Hz, CH2C=C), 3.34(2H, m, CH2NBoc), 3.67(3H, s, OCH3), 3.89(1H, dd, J=5.0, 17.0Hz, CHaHbCO2Me), 4.00(1H, dd, J=6.0, 17.0Hz, CHaHbCO2Me), 4.21-4.16(1H, m, CHNBoc), 5.51(1H, dd, J=7.0, 15.5Hz, CH=C), 5.59-5.72(1H, m, C=CH), 7.35(1H, br. s, NH); Vmax: 3315, 1753, 1685cm^-1; m/z (NH3, CI) 327(M+H⁺, 100%), 299(32%), 288(23%), 271(49%), 227(44%), 226(26%), 96(52%). Found [M+H]⁺ 327.1921. C16H27N205 requires 327.1920.

Preparation of (2'S, 3E)-4-(N-tert-Butoxycarbonylpyrrolidin-2-yl)but-3-enoylglycyl-L-alanine Methyl Ester (20)

(2'S, 3S/R)-4-(N-tert-Butoxycarbonylpyrrolidin-2-yl)-4-oxo-3-phenylsulfonyl butanoyl-glycyl-L-alanine methyl ester (13) (660mg, 1.33mmol) was dissolved in dry methanol (10ml) and the solution cooled to -10degC. Sodium borohydride (170mg, 4.49mmol) was added and the mixture stirred at -10degC under argon until tlc analysis indicated complete consumption of the sulfone (ca. 10min.). Next, anhydrous disodium hydrogenphosphate (2.21g, 15.57mmol) was added, followed immediately by 5% sodium amalgam (4.40g, 9.57mmol). The mixture was allowed to warm to room temperature, stirred for 3h, then filtered and concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate (100ml) and the solution washed sequentially with 1M hydrochloric acid (40ml), sodium bicarbonate (50ml), and water (50ml) then dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate 1:3) to give (2'S, 3E)-4-(N-tert-butoxycarbonylpyrrolidin-2-yl)but-3-enoylglycyl-L-alanine methyl ester (20) (72mg, 16%) as a colourless oil, [alpha]D -16deg (c 1.0, dichloromethane).

Proton Nmr deltaH (300MHz, CDCl3) 1.38(3H, d, J=7.5Hz, CH3), 1.42(9H, s, OC(CH3)3), 2.08-1.53(4H, m, 2xCH2), 2.96(2H, apparent d, J=6Hz, CH2CO), 3.35(2H, m, CH2NBoc), 3.70(3H, s, OCH3), 4.25-4.20(1H, m, CHNBoc), 4.52-4.49(1H, m, CHMe), 5.57-5.48(2H, m including 15.5Hz coupling, CH=CH), 6.79(1H, br. s, NH); Vmax: 3324, 1747, 1679, 1651cm^-1; m/z(NH3, CI) 358(M+NH4⁺, 30%), 341(M+H⁺, 99%), 240(25%), 6(53%). Found [M+H]⁺ 341.2077, C17H29N2O5 requires 341.2076.