1.Design and Use of an Oxazolidine Silyl Enol Ether as a New Homoalanine Carbanion Equivalent for the Synthesis of Carbon-Linked Isosteres of O-Glycosyl Serine and N-Glycosyl Asparagine.
Dondoni A1, Marra A, Massi A. J Org Chem. 1999 Feb 5;64(3):933-944.
A trimethylsilyl enol ether carrying the N-Boc 2,2-dimethyloxazolidine ring was designed to serve as a synthetic equivalent of the homoalanine carbanion for the introduction of the alpha-amino acid side chain at the anomeric carbon of sugars. This new functionalized silyl enol ether was prepared in multigram scale and high enantiomeric purity starting from methyl N-Boc-L-threoninate (six steps, 49% yield). This reagent was employed in two synthetic approaches to C-glycosyl amino acids. In one approach, the BF(3).Et(2)O-promoted coupling with tetra-O-benzyl-D-galactopyranosyl trichloroacetimidate afforded the alpha-linked C-glycoside as main product (30% isolated yield), which upon treatment with tert-butyllithium was converted into the beta-linked isomer. Deoxygenation of these compounds by the Barton-McCombie method and unmasking of the glycyl moiety from the oxazolidine ring by oxidative cleavage with the Jones reagent gave the C-glycosyl serine isosteres alpha- and beta-Gal-CH(2)()-Ser.
2.Studies of peptide antibiotics. XLIII. Syntheses of gramicidin S analogs containing D-serine or dehydroalanine in place of D-phenylalanine and asymmetric hydrogenation of the dehydroalanine residue.
Ando S, Aoyagi H, Waki M, Kato T, Izumiya N. Int J Pept Protein Res. 1983 Mar;21(3):313-21.
Gramicidin S (GS) analogs, [D-Ser4,4']-GS and its precursor [O-benzyl-D-Ser4,4']-GS, were synthesized by the conventional method in order to evaluate the role of the hydroxymethyl side chains in D-Ser at 4,4' positions on the biological activity. Another analog [L-Orn(delta-Boc)2,2',delta Ala4,D-Ser4']-GS was prepared from [D-Ser4,4']-GS by t-butyloxycarbonylation and successive dehydration using dicyclohexylcarbodiimide-CuCl as dehydrating reagent. The delta Ala residue was asymmetrically hydrogenated to D-Ala in the presence of Pd-black. On the microbial assays, [O-benzyl-D-Ser4,4']-GS showed high antimicrobial activity as natural GS, but [D-Ser4,4']-GS showed low activity; the structure-activity relationships of the analogs were discussed.
3.Facile synthesis of N-Fmoc-serine-S-GlcNAc: a potential molecular probe for the functional study of O-GlcNAc.
Ohnishi Y1, Ichikawa M, Ichikawa Y. Bioorg Med Chem Lett. 2000 Jun 5;10(11):1289-91.
A metabolically stable beta-N-acetylglucosaminyl-1-thio-N-Fmoc-serine (S-GlcNAc-Ser) derivative was synthesized in two procedures: one involving a coupling of a readily obtainable 1-pseudo-thiourea of GlcNAc (S-GlcNAc) and iodo-N-Boc-L-alanine benzyl ester, and the other utilizing a modified Mitsunobu reaction of GlcNAc-SH and a serine derivative.
