- Compound instability in dimethyl sulphoxide, case studies with 5-aminopyrimidines and the implications for compound storage and screening
-
The oxidation reactions of 5-aminopyrimidine derivatives in dimethyl sulphoxide (DMSO) were studied. The DMSO solutions of the studied compounds became deeply coloured within a few hours or days. The oxidation products can undergo further condensation reactions with the starting pyrimidines to yield bipyrimidines and/or pyrimidopteridines. The reaction mechanism of the oxidation-condensation reaction was also supported by reactions of the 5-aminopyrimidines with alloxan (2,4,5,6-tetraoxopyrimidine). DMSO is often used as the solvent in in vitro tests of biological activities, but it is also an oxidising agent and may react with solute molecules and significantly affect the quality of the generated biochemical data.
- Prochazkova, Eliska,Jansa, Petr,Brezinova, Anna,Cechova, Lucie,Mertlikova-Kaiserova, Helena,Holy, Antonin,Dracinsky, Martin
-
supporting information
p. 6405 - 6409
(2012/11/07)
-
- Electrophilic Amination of C-H-Acidic Compounds with 1-Oxa-2-azaspirooctane
-
The reactions of 1-oxa-2-azaspirooctane (1, 3,3-pentamethyleneoxaziridine) with malonic (e. g. 4, 35) and cyanoacetic acid derivatives (e. g. 11, 13, 20) and other C-H acids have been studied.After the introduction of a 1-hydroxycyclohexylamino group at the acidic position, five different stabilisation reactions of the intermediate 2 could be classified.The most important one is an intramolecular nucleophilic attack to a nitrile group giving disubstituted 1,4-diazaspiro decanones 2a.Their ring transformations (e. g. 2a -> 3) or the introduction of a second amino group at the same carbon atom (2a -> 3a) are further new reactions.Geminal diamino acid derivatives 3a thus obtained can be stable or rearrange to 3 (R1 = NH2) or eliminate cyclohexanone (formation of 42) and/or ammonia (formation of 41 or 43).Amination of N-cyanoacetyl-protected amino acid esters (20, NHR = amino acid unit) with 1 yields cyclic dipeptide derivatives 41. Key Words: 1-Oxa-2-azaspirooctane / C-H acids / Electrophilic amination / Diamination / Amino acid derivatives / Dehydro peptides
- Andreae, Siegfried,Schmitz, Ernst,Wulf, Jens-Peter,Schulz, Burkhard
-
p. 239 - 256
(2007/10/02)
-