201536-71-2Relevant articles and documents
Synthesis and antiviral evaluation of cyclic and acyclic 2-methyl-3-hydroxy-4-pyridinone nucleoside derivatives
Barral, Karine,Balzarini, Jan,Neyts, Johan,De Clercq, Erik,Hider, Robert C.,Camplo, Michel
, p. 43 - 50 (2007/10/03)
A series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the Vorbrüggen reaction. Iron chelation studies, and antiviral evaluation against a broad panel of viruses, were performed. The pKa value of ligand 25 and the stability constant of the corresponding iron-(III) complex were compared to those of deferiprone. The pFe3+ values were found to be similar. Some compounds showed moderate activity against both wild-type HSV-1 and HSV-2, as well as against a thymidine kinase deficient strain of HSV-1. These results suggest a novel mode of action for this group of nucleoside analogues.
Stereoselective C-glycosylation reactions of ribose derivatives: Electronic effects of five-membered ring oxocarbenium ions
Larsen, Catharine H.,Ridgway, Brian H.,Shaw, Jared T.,Smith, Deborah M.,Woerpel
, p. 10879 - 10884 (2007/10/03)
The factors controlling the highly α-selective C-glycosylation of ribose derivatives were determined by examining the Stereoselective reactions of 18 ribose analogues differing in substitution at C-2, C-3, and C-4. The lowest energy conformers of the intermediate oxocarbenium ions display the C-3 alkoxy group in a pseudoaxial orientation to maximize electrostatic effects. To a lesser extent, the C-2 substituent prefers a pseudoequatorial position, and the alkyl group at C-4 has little influence on conformational preferences. In all cases, the product was formed by stereoelectronically preferred inside attack on the lowest energy conformer.
Synthesis and antiviral evaluation of 3-hydroxy-2-methylpyridin-4-one dideoxynucleoside derivatives
Barral, Karine,Hider, Robert C.,Balzarini, Jan,Neyts, Johan,De Clercq, Erik,Camplo, Michel
, p. 4371 - 4374 (2007/10/03)
We describe the synthesis and the antiviral evaluation of novel α and β dideoxynucleoside derivatives in which the base has been replaced by a 3-hydroxy-2-methylpyridin-4-one. The syntheses were successfully achieved by the use of the standard Vorbrueggen coupling conditions. Moderate activity of these compounds were found on herpes simplex virus (HSV) type 1 and type 2.
Synthetic approach to analogues of the original structure of sclerophytin A
Jung, Michael E.,Pontillo, Joseph
, p. 6848 - 6851 (2007/10/03)
A route to analogues of the original structure of sclerophytin A is described. The β-anomer of dideoxyribosyl nitriles 10a,b (prepared from glutamic acid) was converted into the methyl ketone 11. Addition of a silylated acetylide to 11 in diethyl ether/trimethylamine gave mainly 22a. Alkylation with methallyl halide and ozonolysis gave the ketone 24, which was then converted by hydrogenation and a second ozonolysis into the keto aldehyde 26. A two-step aldol process afforded the desired 3-pyrone 27 in good overall yield. However, several methods for the conversion of this enone 27 into the desired sclerophytin analogue 2 failed.
An enantioselective ring expansion route leading to furanose and pyranose nucleosides featuring spirodiketopiperazines at the anomeric position
Paquette, Leo A.,Brand, Stephen,Behrens, Carsten
, p. 2010 - 2025 (2007/10/03)
A study directed at the enantioselective synthesis of spirodiketopiperazine homologues of hydantocidin is described. Furanoid glycals, systems that are amenable to C-5 metalation in the presence of tert- butyllithium, are readily coupled to N-protected 2,3-azetidinediones provided that at least 1 equiv of BF3·OEt2 is present to curb enolization. The resulting 1:1 mixtures of carbinols undergo smooth ring expansion to spirocyclic keto amides when heated with pyridinium p-toluenesulfonate in benzene. 1,2-Acyl shifts operate exclusively. Since attempts to engage these products in Beckmann rearrangement proved singularly unsuccessful, recourse was alternatively made to new methodology based upon sequential Baeyer- Villiger oxidation and ammonolysis. The data show that the first of these steps occurs with exclusive migration of the quaternary carbon. Furthermore, nucleophilic attack by NH3 can be directed regioselectively to the anomeric region. If heating is supplied during acid-promoted cyclization to the spirodiketopiperazines, spiropyranose derivatives are produced in a complementary process. The central issue of this synthesis effort was the utilization of 4-phenylseleno-substituted furanoid glycals so as to ultimately enable introduction of the cis-diol functionality at C-3 and C-4 (hydantocidin numbering).
Stereoselective Synthesis of Oligo(tetrahydrofurans): Linear and Convergent Routes to Bi- and Tetrahydrofurans
Koert, Ulrich,Stein, Matthias,Wagner, Holger
, p. 1415 - 1426 (2007/10/02)
The "dimeric" and "trimeric" oligo(tetrahydrofurans) (oligo-THFs) 24, 28, 32, and 38 were synthesized stereoselectively according to a linear and a convergent synthetic strategy.The oligo-THFs thus obtained are important intermediates for the synthesis of artificial ion channels.Furthermore, they can be used in the total synthesis of Annonaceae acetogenins, a class of natural occurring oligo-THFs with promising pharmacological properties. - Keywords: Synthesis, stereoselective / Oligo(tetrahydrofurans), natural, non-natural /Ion channels, artificial / Annonaceae acetogenins
Tetrahydrofuran-podands, stereoselective synthesis of trans-2,5-oligo-tetrahydrofurans
Koert, Ulrich,Stein, Matthias,Harms, Klaus
, p. 2299 - 2302 (2007/10/02)
Enantiomerically pure THF-podands 1 were synthesized along a linear route starting from lactone 3. A high degree of stereochemical control was achieved by chelation controlled addition of the functionalized Grignard reagent 7 to α-alkoxy-aldehydes of type 6.
Synthesis and evaluation of a series of 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)thymines.
Agyei-Aye,Baker
, p. 261 - 275 (2007/10/02)
A series of 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)thymines (3'-alkyl-3'-deoxythymidines) has been prepared from 5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-D-glycero-pent-2- enono-1,4-lactone ((S)-5-[(tert-butyldiphenylsilyl)oxymethyl]-2(5H)- furanone) by Michael addition of the appropriate organocopper reagent, followed by reduction of the lactone, acetylation of the resulting hemiacetal, and trimethylsilyl triflate-catalyzed coupling with 2,4-di-O-(trimethylsilyl)thymine. The protected nucleosides were desilylated by using tetrabutylammonium fluoride to give anomeric mixtures of the free nucleosides. The unsubstituted 2',3'-dideoxynucleoside analog was similarly prepared from 5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-D-glycero-pentono- 1,4-lactone ((S)5-[(tert-butyldiphenylsilyl)-oxymethyl]-dihydro-2(3H)-fu r anone).
