4'-Hydroxy-3-methoxyflavones are natural compounds with known antiviral activities against picornaviruses such as poliomyelitis and rhinoviruses. In order to establish a structure-activity relationship a series of analogues were synthesized, and their antiviral activities and cytotoxicities were compared with those of flavones from natural origin. The 4'-hydroxyl and 3-methoxyl groups, a substitution in the 5 position and a polysubstituted A ring appeared to be essential requirements for a high activity. The most interesting compound was 4',7-dihydroxy-3-methoxy-5,6-dimethylflavone possessing in vitro TI99 values of greater than 1000 and greater than 200 against poliovirus type 1 and rhinovirus type 15, respectively. This compound was also active against other rhinovirus serotypes (2, 9, 14, 29, 39, 41, 59, 63, 70, 85, and 89) tested, having MIC50 values ranging from 0.016 to 0.5 micrograms/mL. Finally in contrast to quercetin it showed to be not mutagenic in concentrations up to 2.5 mg in the Ames test.
No protecting groups are required for the cross‐coupling of N‐monosubstituted α‐aminonitriles with imines. Depending on the workup procedure, highly substituted unsymmetrical 1,2‐diamines or 1,2‐diimines can be prepared in a one‐pot procedure. The diastereoselective reduction of the diimines furnishes either the syn‐ or the anti‐configurated diamines (see scheme).
The reaction of alpha,beta-unsaturated carbonyl compounds with aminoacetonitrile hydrochloride furnishes 3,5-disubstituted 3,4-dihydro-2H-pyrrole-2-carbonitriles in a one-pot reaction sequence. While these products can serve as starting materials for the preparation of polysubstituted pyrrolizidines, they are kinetically stable against the base-induced elimination of HCN. In contrast, their 2-substituted analogues obtained from alpha-substituted alpha-aminonitriles can be readily converted to the corresponding 2,3,5-trisubstituted pyrroles under microwave irradiation. The key step presumably involves the thermal electrocyclization of a stabilized 2-azapentadienyl anion formed by condensation of the reactants and subsequent deprotonation.
A straightforward access to crispine A and C-ring-substituted analogs by 1,4-addition of a deprotonated α-amino nitrile to α,β-unsaturated carbonyl compounds is described. If the reduction step is omitted, substituted 5,6-dihydropyrrolo[2,1-a]isoquinolines can be obtained.
Ohne Schutzgruppen gelingt die Kreuzkupplung von N‐monosubstituierten α‐Aminonitrilen mit Iminen. Je nach Aufarbeitung der Reaktionsmischung können so im Eintopfverfahren unsymmetrische hochsubstituierte 1,2‐Diamine oder 1,2‐Diimine erhalten werden. Durch diastereoselektive Reduktion der Diimine sind wahlweise die syn‐ oder die anti‐konfigurierten Diamine zugänglich (siehe Schema).
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