From D-glucose to biologically potent L-hexose derivatives: synthesis of alpha-L-iduronidase fluorogenic detector and the disaccharide moieties of bleomycin A2 and heparan sulfate.
A novel and convenient route for the synthesis of biologically potent and rare L-hexose derivatives from D-glucose is described. Conversion of diacetone-alpha-D-glucose (14) into 1,2:3,5-di-O-isopropylidene-beta-L-idofuranose (19) was efficiently carried out in two steps. Orthogonal isopropylidene rearrangement of compound 19 led to 1,2:5,6-di-O-isopropylidene-beta-L-idofuranose (27), which underwent regioselective epimerization at the C3 position to give the L-talo- and 3-functionalized L-idofuranosyl derivatives. Hydrolysis of compound 19 under acidic conditions furnished 1,6-anhydro-beta-L-idopyranose (35) in excellent yield, which was successfully transformed into the corresponding L-allo, L-altro, L-gulo, and L-ido derivatives via regioselective benzylation, benzoylation, triflation and nucleophilic substitution as the key steps. Applications of these 1,6-anhydro-beta-L-hexopyranoses as valuable building blocks to the syntheses of 4-methylcoumarin-7-yl-alpha-L-iduronic acid and the disaccharide moieties of bleomycin A(2) as well as heparan sulfate are highlighted.
Lee
Jinq-Chyi
JC
Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
Chang
Shu-Wen
SW
Liao
Chih-Cheng
CC
Chi
Fa-Chen
FC
Chen
Chien-Sheng
CS
Wen
Yuh-Sheng
YS
Wang
Cheng-Chung
CC
Kulkarni
Suvarn S
SS
Puranik
Ramachandra
R
Liu
Yi-Hung
YH
Hung
Shang-Cheng
SC
D001761:Bleomycin / Q000138:chemical synthesis / Q000737:chemistry*; D004187:Disaccharides / Q000138:chemical synthesis*; D005947:Glucose / Q000737:chemistry*; D006497:Heparan Sulfate / Q000138:chemical synthesis / Q000737:chemistry*; D006601:Hexoses / Q000138:chemical synthesis*; D007067:Iduronic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D007068:Iduronidase / Q000138:chemical synthesis*; D008968:Molecular Conformation
D001761:Bleomycin; D004187:Disaccharides; D005947:Glucose; D006497:Heparan Sulfate; D006601:Hexoses; D007067:Iduronic Acid; D007068:Iduronidase; C010997:idose