Fmoc-O-benzyl-L-serine

Mercuric bromide-promoted glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-alpha-D-glucopyranosyl chloride in refluxing 1,2-dichloroethane gave the corresponding beta-glycosides in good yields (64 and 62%, respectively). Direct coupling of the commercially available Fmoc-Ser-OH and Fmoc-Thr-OH carboxylic acids under similar conditions gave the corresponding beta-glycosides, possessing free carboxyl groups, in moderate yields (50 and 40%, respectively).

N-Troc-protected (Troc = 2,2,2-trichloroethoxycarbonyl) glucosamine and galactosamine glycosyl donors (1-O-acetyl sugar, bromo sugar, and thioglycoside) were compared with the corresponding N-Phth-protected derivatives in glycosylations of 2-(trimethylsilyl)ethanol, 2-bromoethanol, methyl 3-mercaptopropionate, N-Fmoc-protected serine, and 2-(trimethylsilyl)ethyl 6-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside. The N-Troc-protected donors gave pure beta-glycosides in somewhat higher yields than the N-Phth-protected counterparts. The N-Troc protecting group can be removed by reduction with zinc, which allows selective N-deprotection in oligosaccharides containing both N-Troc and N-Phth groups.

A synthetic strategy for the preparation of two orthogonally protected methyl esters of the non-proteinogenic amino acid 2,3-l-diaminopropanoic acid (l-Dap) was developed. In these structures, the base-labile protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) was paired to the p-toluensulfonyl (tosyl, Ts) or acid-labile tert-butyloxycarbonyl (Boc) moieties. The synthetic approach to protected l-Dap methyl esters uses appropriately masked 2,3-diaminopropanols, which are obtained via reductive amination of an aldehyde prepared from the commercial amino acid Nα-Fmoc-O-tert-butyl-d-serine, used as the starting material. Reductive amination is carried out with primary amines and sulfonamides, and the process is assisted by the Lewis acid Ti(OiPr)4. The required carboxyl group is installed by oxidizing the alcoholic function of 2,3-diaminopropanols bearing the tosyl or benzyl protecting group on the 3-NH2 site. The procedure can easily be applied using the crude product obtained after each step, minimizing the need for chromatographic purifications. Chirality of the carbon atom of the starting d-serine template is preserved throughout all synthetic steps.