[Synthetic studies on sugar-related bioactive substances based on the ring transformation].
The development of two novel ring conversions of sugar derivatives is described. The first is an efficient conversion of 5-enopyranosides and 6-O-acetyl-5-enopyranosides to the corresponding substituted cyclohexanones mediated by a catalytic amount of palladium dichloride. After a survey of various substrates, the reaction was confirmed to be general and useful. Syntheses of bioactive compounds utilizing this method were therefore investigated. Cyclophellitol, which is a potent beta-glucoidase inhibitor, and its diastereoisomer were efficiently synthesized. Furthermore, novel synthesis of all enantiomerically pure diastereoisomers of inositol starting with 6-O-acetyl-5-enopyranosides was investigated. Good accessibility of these enantiomerically pure inositol diastereoisomers results in the efficient syntheses of D-myo-inositol 1,4,5-trisphosphate and D-myo-inositol 1,3,4,5-tetrakisphosphate. The second investigation involved novel and efficient conversion of D-glycono-1,5-lactones into the corresponding L-sugars. The important intermediate, delta-hydroxyalkoxamate, was provided by a practical alkoxyamination of D-glycono-1,5-lactones mediated by Me3Al. In contrast to the preparation of beta-lactam skeletons from beta-hydroxyalkoxamates, the cyclization of delta-hydroxyalkoxamates under Mitsunobu conditions resulted in O-alkylation rather than N-alkylation. It is noteworthy that delta-hydroxyalkoxamates derived from D-mannono-1,5-lactones afforded the O-alkylation product in 91% yield. No N-alkylation product was detected in this case. These O-cyclized oximes, in which the inversion of the configuration at C5 was secured, were efficiently converted into L-sugars.
Takahashi
Hideyo
H
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195. hide-tak@pharm.teikyo-u.ac.jp
D002241:Carbohydrates / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003511:Cyclohexanols / Q000138:chemical synthesis / Q000737:chemistry; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D007294:Inositol / Q000138:chemical synthesis; D007295:Inositol Phosphates / Q000138:chemical synthesis; D007783:Lactones; D010165:Palladium
D002241:Carbohydrates; D003511:Cyclohexanols; D003512:Cyclohexanones; D007295:Inositol Phosphates; D007783:Lactones; C063285:cyclophellitol; D007294:Inositol; D010165:Palladium; C008756:palladium chloride