Synthesis of N-Fmoc-O- (N‘-Boc-N‘-methyl)-aminohomoserine, an Amino Acid for the Facile Preparation of Neoglycopeptides

Abstract

The synthesis of N-Fmoc-O-(N'-Boc-N'-methyl)-aminohomoserine in 35% overall yield from l-homoserine is described. This amino acid can be efficiently incorporated into peptides using Fmoc-chemistry-based solid-phase peptide synthesis, and the resulting peptides can be chemoselectively glycosylated at the aminooxy side chains to generate neoglycopeptides. The synthesis of this derivative greatly expands the availability of a previously developed neoglycopeptide synthesis strategy.

The Identification of Perillyl Alcohol Glycosides with Improved Antiproliferative Activity

“…The inclusion of azidosugars served as a starting point for subsequent divergence via chemoselective modification [via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition] 35,36 or selective reduction to afford the corresponding aminosugar conjugates (Scheme 2). 30,32,37−39 A library of 34 distinct neoglycosides ( PG1 – PG34 ) were synthesized (Figure S1 and Table S1 in Supporting Information) in good to excellent yields (23–82%), with the β-anomer as predominate product in most cases, consistent with previous studies. 40−49 For aminosugar conjugates, azidosugar glycosides ( PG2 , PG8 , PG9 , PG13 ) were readily reduced to their corresponding aminosugar counterparts ( PG7 , PG10 , PG11 , PG19 ) in the presence of PMe 3 (1.0 M in THF), with yields ranging from 29 to 46%.…”

Site-specific labeling of synthetic peptide using the chemoselective reaction betweenN-methoxyamino acid and isothiocyanate

“…Along this line, the chemoselectivity of the N ‐alkylaminooxy group with electrophiles, such as succinimidyl ester, activated haloalkanes, has been examined . In addition, N ‐alkylaminooxy groups have been extensively studied for the chemoselective glycosylation to create glycoconjugates and glycopeptides . These functional groups retain pKa (4–5) significantly lower than that of the α ‐amino group (about 9.1) and the ε ‐amino group of Lys residue (about 10.5), which is the basis of the chemoselectivity.…”

Opioid peptides: synthesis and biological properties of [(Nγ-glucosyl,Nγ-methoxy)-α,γ-diamino-(S)-butanoyl]4-deltorphin-1-neoglycopeptide and related analogues

“…8- 16 A new type of chemoselective glycosylation by reaction of unprotected reducing sugars with any derivatized peptide containing a N,O-di-substituted hydroxylamine side chain function (R 1 -NH-O-R 2 ) has been described. 17,18 In previous papers 19, 20 we described the synthesis of some dermorphin and deltorphin analogues β-O-and α-C-glycosylated on the C-terminal amino acid residue and reported their opioid receptor affinity and their analgesic potency after † With the exception of -Ala the amino acid residues are of -configuration. Standard abbreviations for amino acid derivatives and peptides are according to the suggestions of the IUPAC-IUB Commission on Biochemical Nomenclature, Eur.…”