129430-93-9Relevant articles and documents
Enantioselective synthesis and physicochemical properties of libraries of 3-amino- and 3-amidofluoropiperidines
Orliac, Aurelie,Routier, Julie,Burgat Charvillon, Fabienne,Sauer, Wolfgang H. B.,Bombrun, Agnes,Kulkarni, Santosh S.,Gomez Pardo, Domingo,Cossy, Janine
, p. 3813 - 3824 (2014/04/03)
The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pK a due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H+ and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pK a between cis- and trans-3-amino-5-fluoropiperidines.
The synthesis and biological activity of C2-fluorinated pyrrolo[2,1-c][1,4]benzodiazepines
O'Neil, Ian A.,Thompson, Stephen,Kalindjian, S. Barret,Jenkins, Terence C.
, p. 7809 - 7812 (2007/10/03)
The novel C2-fluorinated pyrrolobenzodiazepines (1, 2 and 3) have been prepared from commercially available trans-hydroxyproline in good overall yield and were screened for in vitro cytotoxicity against a number of cancer cell lines. The 2R-fluoro isomer 2 exhibits an activity of 76 nM against the CH1 cell line.
Simple Synthesis of cis-4-Hydroxy-L-proline and Derivatives Suitable for Use as Intermediates in Peptide Synthesis
Papaioannou, Dionissios,Stavropoulos, George,Karagiannis, Kostas,Francis, George W.,Brekke, Trond,Aksnes, Dagfinn W.
, p. 243 - 251 (2007/10/02)
An intramolecular Mitsunobu reaction in the presence of triphenylphosphine - diethyl azodicarboxylate (TPP-DEAD) resulted in the conversion of trans-4-hydroxy-N-trityl-L-proline to 5-triphenylmethyl-2-oxa-5-aza-bicycloheptan-3-one.This bicyclic lactone proved to be a key intermediate in the synthesis of cis-4-hydroxy-L-proline and derivatives thereof.TPP-DEAD-catalysed methanolysis of the key lactone gave the methyl ester of cis-4-hydroxy-N-trityl-L-proline, while ammonolysis in isopropyl alcohol provided the corresponding amide. p-Toluene-sulfonic acid treatmen t of the lactone, ester and amide led to detritylation and formation of the corresponding p-toluenesulfonates.Saponification of the key intermediate provided cis-4-hydroxy-N-trityl-L-proline which was first benzylated and then elaborated to the 1-hydroxybenzotriazolyl ester.This last ester and the three p-tolenesulfonates preparared above were utilised for the incorporation of cis-4-hydroxy-L-proline in the synthesis of model peptides.