ABSTRACT
Stereoselective and efficient synthesis of hydroxymethyl-substituted rac-quercitols (13-15) was achieved, starting from cis-furan (Kobayashi, 2008) with photooxygenation reaction, which is readily available by the reduction of cis-phtalic anhydride. α- and ß-Glucosidase enzyme activity of the target molecules was evaluated and good inhibitor activity was seen. One- and two-dimensional NMR spectroscopy, IR spectroscopy and X-ray crystallography were utilized in the structure characterization of products.
Subject(s)
Glucosidases/antagonists & inhibitors , Glycoside Hydrolase Inhibitors/pharmacology , Inositol/analogs & derivatives , Crystallography, X-Ray , Dose-Response Relationship, Drug , Glucosidases/metabolism , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , Humans , Inositol/chemical synthesis , Inositol/chemistry , Inositol/pharmacology , Models, Molecular , Molecular Structure , Stereoisomerism , Structure-Activity RelationshipABSTRACT
4,5-Dimethylenecyclohex-1-ene was subjected to a photooxygenation reaction to introduce oxygen functionalities. The endoperoxide obtained underwent an ene-reaction to form hydroperoxides with 1,3-diene structures. Further addition of singlet oxygen to the diene units resulted in the formation of tricyclic hydroperoxides having three oxygens in the molecule. Cleavage of the oxygen-oxygen bonds followed by epoxidation of the remaining C-C double bond and concomitant ring-opening reaction furnished the isomeric carbasugars.
Subject(s)
Carbasugars/chemical synthesis , Cyclohexenes/chemistry , Carbasugars/chemistry , Hydrogen Peroxide/chemistry , Molecular Structure , Oxidation-Reduction , Singlet Oxygen/chemistry , StereoisomerismABSTRACT
The efficient synthesis of gala-, epi-, neo-, and muco-quercitols and some brominated quercitols starting from cyclohexa-1,4-diene is reported. Treatment of the dibromide, obtained by the addition of bromine to cyclohexa-1,4-diene, with m-chloroperbenzoic acid (m-CPBA) yielded the dibromoepoxide, which was successfully converted to the desired dibromodiol by treatment with sulfuric acid. The resulting diol was reacted with 2,2-dimethoxypropane to give the dibromoketal. Hydrogen bromide elimination with NaOMe gave the key compound methoxyketal, rel-(3aS,5R,7aS)-5-methoxy-2,2-dimethyl-3a,4,5,7a-tetrahydrobenzo[d][1,3]dioxole. The second key compound, an isomeric methoxyketal, was prepared by ketalization of 4,5-dibromocyclohexane-1,2-diol with dimethoxypropane followed by the reaction with NaOMe. Deprotection of ketal functionality with sulfuric acid followed by acetylation with acetic anhydride in pyridine resulted in the formation of diacetate rel-(1S,2R,5R)-5-methoxycyclohex-3-ene-1,2-diyl diacetate. Epoxidation of the double bonds in isomeric methoxy diacetates and cis-hydroxylation followed by epoxide-opening and deprotection resulted in the formation of various quercitol derivatives. The inhibition activity of eleven quercitols, methoxyquercitols and bromoquercitols was tested against α-glycosidase.
Subject(s)
Cyclohexenes/chemistry , Inositol/chemical synthesis , Inositol/analogs & derivatives , Inositol/chemistry , Molecular Conformation , StereoisomerismABSTRACT
1,3,3a,7a-Tetrahydro-2-benzofuran was used as key compound for the synthesis of various bishomoinositol derivatives. The diene was subjected to an epoxidation reaction for further functionalization of the diene unit. The bisepoxide obtained was submitted to a ring-opening reaction with acid in the presence of water. Various bishomoinositols were synthesized. However, when the reaction was carried out in the presence of acetic anhydride, a substituted 3-oxabicyclo[3.3.1]nonane skeleton was formed. The mechanism of the formation of the products is discussed.
