Synthesis of Urea and Carbamate Glycosides Employing Unprotected Carbohydrates

Abstract

A study of methods for the synthesis of urea and carbamate glycosides, starting with unprotective carbohydrates, led to the preparation of amino acid-carbohydrate conjugates in aqueous ­media.

Key words

neoglycoconjugates - urea - carbamate - glucose - glucosamine

References and Notes

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10

A solution of d-glucose (300 mg, 1.67 mmol) and 1-n-butylurea (387 mg, 3.33 mmol) in a mixture of 2.4 M HCl (0.25 mL) and MeCN (1.0 mL) was stirred at 50 ˚C for 24 h. The mixture was neutralized by the addition of NaHCO₃ and washed with CH₂Cl₂ to remove excess 1-n-butylurea. The resulting aqueous layer was extracted with n-butanol. The combined n-butanol extracts were concentrated under reduced pressure to afford the crude 1-n-butyl-3-glucosyl-urea, which was treated with a mixture of acetic anhydride (5.0 mL) and pyridine (10 mL) at 50 ˚C for 3 h. After standard workup followed by chromatographic purification, a mixture of acetyl β-1-n-butyl-3-glucosylurea and acetyl
α-1-n-butyl-3-glucosylurea 12 (507 mg, β/α = 92:8) was obtained in 68% yield. Concentration of CH₂Cl₂ extracts and purification by chromatography provided the recovered 1-n-butylurea (210 mg). The yield of 1-n-butyl-3-glucosylureas 12 based on the consumed 1-n-butylurea was calculated to be 75%.

12

Urea glucosamide 23 was reported to be synthesized from isonitrile 26 prepared from N-acetyl-d-glucosamine 22 in five steps (Scheme  [9] ). See reference 2f.

Scheme 9

13

These types of N-glycosyl carbamates were synthesized by the reaction of glycosyl isocyanates with alcohols. Authentic samples of 24 and 25 were prepared by the reaction of n-butyl alcohol with glucosyl isocyanates, generated from glucosyl isonitriles 5 and 8. See reference 2d.