Synthesis of (+/-)-madindolines and chemical models. Studies of chemical reactivity.
[reaction: see text] The madindolines are believed to inhibit cytokine signaling through the gp130 receptor. Model compounds of madindolines were synthesized and tested for thiol reactivity. The heterocyclic moiety of madindoline was shown to form thiol adducts via the Savige-Fontana reaction. The enedione moiety was found to be unreactive toward simple thiols unless the quaternary center was removed. Using the powerful Moore reaction, we have synthesized (+/-)-madindoline A and B in 11 steps.
McComas
Casey C
CC
Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
Perales
Joe B
JB
Van Vranken
David L
DL
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D058966:Contactins; D003500:Cyclization; D003543:Cysteamine / Q000737:chemistry; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry; D008352:Mannich Bases / Q000737:chemistry; D008958:Models, Molecular; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
D019086:Bridged Bicyclo Compounds, Heterocyclic; D058966:Contactins; D007202:Indicators and Reagents; D007211:Indoles; D008301:Maleimides; D008352:Mannich Bases; D019006:Neural Cell Adhesion Molecules; D013438:Sulfhydryl Compounds; C103158:madindoline A; D003543:Cysteamine