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.

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%.

11 Ichikawa Y. Morishita Y. Kusaba S. Sakiyama N. Matsuda Y. Nakano K. Kotsuki H. Synlett  2010,  1815 

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.