Preparation of l-serine and l-cystine stereospecifically labeled with deuterium at the β-position

The synthesis of l-serine and l-cystine stereospecifically labeled with deuterium at the β-position is described. The carboxyl group of d-serine was transformed into chirally deuterium-labeled alcohol via asymmetric reduction of 1-deuterio aldehyde, while the original hydroxymethyl group was converted into a carboxyl functionality to afford (2S,3R)-[3-2H]serine. Functional group interconversions of the hydroxyl group in the obtained deuterium-labeled l-serine gave (2R,2′R,3S,3′S)-[3,3′-2H2]cystine.

Figure optionsDownload as PowerPoint slide

(1R)-[1-[(3,5-Dimethylpyrazol-1-yl)carbonyl]-2-benzyloxyethyl]carbamic acid tert-butyl esterC20H27N3O4[α]D26=+18.2 (c 1.0, CHCl3)Source of chirality: d-SerAbsolute configuration: (1R)

(2R,3R)-N-tert-Butoxycarbonyl-O3-acetyl[3-2H]serinolC10H182HNO5[α]D26=+3.2 (c 1.0, CHCl3)Source of chirality: d-Ser and S-Alpine-BoraneAbsolute configuration: (2R,3R)

(2S,3R)-N-tert-Butoxycarbonyl-O3-acetyl[3-2H]serine tert-butyl esterC14H242HNO6[α]D26=+24.05 (c 1.0, CHCl3)Source of chirality: d-Ser and S-Alpine-BoraneAbsolute configuration: (2S,3R)

(2R,2′R,3S,3′S)-[3,3′-2H2]CystineC6H102H2N2O4S2[α]D23=-220.0 (c 0.1, 1 M HCl)Source of chirality: d-Ser and S-Alpine-BoraneAbsolute configuration: (2R,2′R,3S,3′S)

(2S,3R)-[3-2H]SerineC3H62HNO3Ee = 94%[α]D23=+15.4 (c 1.0, 1 M HCl)Source of chirality: d-Ser and S-Alpine-BoraneAbsolute configuration: (2S,3R)