Synthesis of 1-deoxy-1-hydroxymethyl- and 1-deoxy-1-epi-hydroxymethyl castanospermine as new potential immunomodulating agents.
Two new C-1 epimeric hydroxymethyl castanospermine congeners 2a and 2b, synthesized by stereocontrolled intramolecular double reductive amination of D-glucose derived beta-keto ester as a key step, showed impressive immuno-potentiating property. The bioactivity was mediated through up-regulation of T(H1)/T(H2) cytokine ratio. The finding suggested that immunmodulatory activity of polyhydroxylated indolizidine alkaloids can be tuned by minor structural/stereochemical alterations.
Vyavahare
Vinod P
VP
Garware Research Centre, Department of Chemistry, University of Pune, Pune-411 007, India.
Chakraborty
Chaitali
C
Maity
Biswanath
B
Chattopadhyay
Subrata
S
Puranik
Vedavati G
VG
Dhavale
Dilip D
DD
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D013154:Spleen / Q000166:cytology; D013237:Stereoisomerism; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054836:Indolizidines
D000276:Adjuvants, Immunologic; D003208:Concanavalin A; D016207:Cytokines; D007212:Indolizines; C524717:1-(hydroxymethyl)-6,7,8-trihydroxyindolizidine; C037806:castanospermine; D054836:Indolizidines