Réaction #168514

Équation de réaction

D-(+)-xylose

hydrochloride

N-{4-[4-(2-aminoethoxy)phenyl]butyl}-N′-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)guanidine

sodium cyanoborohydride

→

compound 23

Rendement 20.6%

N-[4-(4-{2-[bis-((2R,3S,4R)-2,3,4,5-tetrahydroxypentyl)amino]ethoxy}-phenyl)butyl]-N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidine dihydrochloride

Rendement 20.6%

Solvants

methanol

Conditions de réaction

Traitement

1. 1
   TempératureThen the solution was cooled to −78° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred at −78° C. for 2 h and at room temperature for 4 d
3. 3
   AutreAfter this time, the solvent was removed under reduced pressure
4. 4
   Lavagethe residue was washed with water
5. 5
   AutreThe formed yellow solid was isolated
6. 6
   Autredried under vacuum
7. 7
   workup.DISSOLUTIONThen the residue was re-dissolved in 5% HCl
8. 8
   Autrethe solvent was removed at reduced pressure
9. 9
   workup.DISSOLUTIONThe obtained compound was dissolved in water containing 0.1% TFA
10. 10
    Autrepurified by preparative HPLC (C 18 Luna column from Phenomenex 250×21.2 mm, 5μ, isocratic method, water/acetonitrile=80%:20%)
11. 11
    workup.ADDITIONThe fractions containing the target compound
12. 12
    Autrethe solvent was removed under reduced pressure
13. 13
    workup.DISSOLUTIONThe residue was dissolved in 5% HCl
14. 14
    Autresolvent was removed under reduced pressure (twice)
15. 15
    workup.DISSOLUTIONThe resulting yellow powder was dissolved in water

Mode opératoire

D-(+)-xylose (0.35 g, 2.6 mmol) was added to a solution of hydrochloride 4 (0.3 g, 0.65 mmol) in methanol (20 mL) and the mixture was stirred for 20 min at room temperature. Then the solution was cooled to −78° C. and sodium cyanoborohydride (0.17 g, 2.6 mmol) was added. The reaction mixture was stirred at −78° C. for 2 h and at room temperature for 4 d. After this time, the solvent was removed under reduced pressure and the residue was washed with water. The formed yellow solid was isolated and dried under vacuum. Then the residue was re-dissolved in 5% HCl and the solvent was removed at reduced pressure. The obtained compound was dissolved in water containing 0.1% TFA and purified by preparative HPLC (C 18 Luna column from Phenomenex 250×21.2 mm, 5μ, isocratic method, water/acetonitrile=80%:20%). The fractions containing the target compound were combined and the solvent was removed under reduced pressure. The residue was dissolved in 5% HCl and solvent was removed under reduced pressure (twice). The resulting yellow powder was dissolved in water and the solution was lyophylized to give 34 mg (7%) of compound 23 as a yellow solid. 1H NMR (300 MHz, CD3OD) δ 1.64 (br s., 4H), 2.62 (m, 2H), 3.30 (m, 4H), 3.35-3.70 (m, 13H), 4.23 (m, 2H), 4.47 (m, 2H), 6.95 (d, 2H), 7.15 (d, 2H). m/z (APCI)=689 [C28H45ClN8O10+H]+. [α]D25=−16.1° (c=0.5, MeOH).

Source