19895-66-0Relevant articles and documents
CuAAC click chemistry with N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol provides access to triazole-linked piperidine and azepane pseudo-disaccharide iminosugars displaying glycosidase inhibitory properties
Zamoner, Luís Otávio B.,Arag?o-Leoneti, Valquíria,Mantoani, Susimaire P.,Rugen, Michael D.,Nepogodiev, Sergey A.,Field, Robert A.,Carvalho, Ivone
, p. 29 - 37 (2016)
Protecting group-free synthesis of 1,2:5,6-di-anhydro-D-mannitol, followed by ring opening with propargylamine and subsequent ring closure produced a separable mix of piperidine N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and azepane N-propargyl 1,6-dideo
Iminosugars: Effects of stereochemistry, ring size, and n-substituents on glucosidase activities
Zamoner, Luís O. B.,Arag?o-Leoneti, Valquiria,Carvalho, Ivone
, (2019/09/03)
N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 μM and 138 μM, respectively, using DNJ as reference (IC50 134 μM). On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 μM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 μM). Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 μM) of the corresponding D-gluco-piperidine miglustat drug (40a). Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 μM.
Solid phase synthesis of (R)- and (S)-[13C]-butadiene monoxide
Claffey, David J.,Ruth, James A.
, p. 3715 - 3716 (2007/10/03)
A stereospecific route to (R)- and (S)-[13C]-butadiene monoxide was developed using (R)- or (S)- glycidaldehyde and a polymer-supported Wittig reagent.
Mechanisms of formation of adducts from reactions of glycidaldehyde with 2′-deoxyguanosine and/or guanosine
Golding, Bernard T.,Slaich, Pritpal K.,Kennedy, Gordon,Bleasdale, Christine,Watson, William P.
, p. 147 - 157 (2007/10/03)
Convenient syntheses of rac-glycidaldehyde from rac-but-3-ene-1,2-diol and (R)-glycidaldehyde from D-mannitol are described. (R)-Glycidaldehyde (1) reacts with guanosine in water (pH 4-11, faster reaction at higher pH) to give initially 6(S)-hydroxy-7(S)-(hydroxymethyl)-3-(β-D-ribofuranosyl)-5,6,7- trihydroimidazo[1,2-a]purin-9(3H)-one (7a) and 6(S),7(R)-dihydroxy-3-(β-D-ribofuranosyl)-5,6,73-tetrahydropyrimido[1,2-a] purin-10(3H)-one (8a). The former decomposes to 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(β-D-ribofuranosyl)imidazo[1,2-a] purine (3a), 5,9-dihydro-9-oxo-3-(β-D-ribofuranosyl)imidazo[1,2-a]purine (5a, 1,N2-ethenoguanosine), and formaldehyde, while the latter adduct is relatively stable. The position of the hydroxymethyl group on the imidazo ring of 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(β-D-ribofuranosyl)imidazo-[1,2-a] purine was proved by 13C NMR analysis of adducts derived from [1-15N]guanosine and [amino-15N]guanosine. At longer reaction times, the adduct 7,7′-methylenebis[5,9-dihydro-9-oxo-3-(β-D-ribofuranosyl)imidazo[1,2- a]purine[ (4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by 13C NMR analysis of the 15N-labeled adduct derived from [1-15N]guanosine. Analogous adducts were obtained from the reaction between glycidaldehyde and deoxyguanosine. Mechanisms of formation of the adducts from glycidaldehyde and guanosine/deoxyguanosine are proposed and supported by model studies with simple amines. The formaldehyde produced in the reactions described reacts with guanosine to give the known adduct N2-(hydroxymethyl)guanosine (9).
