Expeditious Synthesis of β-Linked Glycosyl Serine Methylene Isosteres (β-C-Gly Ser) via Ethynylation of Sugar Lactones

Abstract

The addition of the lithium derivative of N-Boc 4-ethynyl-2,2-dimethyl-1,3-oxazolidine to tetra-O-benzyl-d-gluco- and galactonolactone and 2-azido-2-deoxy congeners afforded the corresponding ethynyl ketoses in fairly good yields (64-78%). Following the conversion of the ketoses into O-acetates and removal of the acetoxy group by silane reduction, the resulting β-linked ethynyl glycosides were transformed into N-Boc C-glycosyl α-aminobutyric acids by reduction of the triple bond using H₂/Pd(OH)₂ and oxidative cleavage of the oxazolidine ring using the Jones’ reagent. After the removal of O-benzyl groups of the carbohydrate moieties by hydrogenation and the reduction of azido to amino group, all compounds were subjected to acetylation and isolated as O- and N-acetyl derivatives. The C-glycosyl α-amino acids prepared correspond to methylene isosteres of O-glycosyl serines.

Key words

alkynyl glycosides - glycopeptides - C-glycosides - C-glycosyl amino acids

References

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12

Evidently the alkyne 1 {[α]_D +90 (c = 0.7, CHCl₃)} is the enantiomer of the product described in Ref. [10] which in fact was prepared starting from l-serine. Therefore the optical rotation value quoted in Ref. [10] {([α]_D +88 (c = 1.05, CHCl₃)} should be changed into a negative value in agreement with earlier data from the literature quoted in the same publication.