The Amadori rearrangement as key reaction for the synthesis of neoglycoconjugates

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

“…Aldoheptose 10 was taken to the Amadori rearrangement without further purification. Three typical amines, dibenzylamine, 6-aminohexanol as well as 6-aminohexanoic acid methyl ester hydrochloride were investigated [25]. In all cases the corresponding Amadori products 11 , 12 as well as 13 were formed, which was confirmed by comparison of the NMR data [25].…”

“…After purification, 1-(5-(methoxycarbonyl)pentylamino-1-deoxy-α-D- galacto -hept-2-ulose was also obtained as a mixture of pyranoid 25a and furanoid 25b forms with a 5:1 ratio and a combined yield of 35%. The Amadori products featuring a secondary amine at position C-1, compounds 24 and 25 , were further reacted with triphosgene [25]. In this reaction, the anomeric hydroxy group and the amine at position C-1 formed a cyclic carbamate, thereby stabilising the hemiacetal at the anomeric position.…”

“…General method A (Amadori rearrangement with free amines) [25] : The respective aldose was dissolved in abs. EtOH, and then 1.2 equiv of the free amine and 1.2 equiv of AcOH were added, and the reaction mixture was stirred at 40 °C until TLC showed satisfactory conversion of the starting material.…”

“…General method B (Amadori rearrangement with amine hydrochlorides) [25] : The respective amine hydrochloride was dissolved in abs. EtOH, 1 equiv of Et 3 N was added, and the mixture was stirred for 20 min at rt.…”

“…We have succeeded in optimising the reaction conditions for the Amadori rearrangement when introducing D- glycero -D- gulo -aldoheptose as the starting material. In this special case, all substituents of the resulting 1-aminodeoxy ketose adopt an equatorial position in the 5 C 2 pyranoid conformation, which is a strong driving force providing excellent preparative yields [25]. In general, this reaction leads to non-natural C -glycosyl type glycoconjugates, which are of particular interest for biological investigation because of their chemical stability towards physiological hydrolysis of the glycosidic linkage, compared to the naturally occurring O - as well as N -glycosides [26].…”