ABSTRACT
Indolizidine and quinolizidine derivatives are readily assembled from proline or pipecolic acid and γ-nitroaldehydes by means of a decarboxylative annulation process. These reactions are promoted by simple acetic acid and involve azomethine ylides as reactive intermediates. The method was applied to the synthesis of an epiquinamide analog.
Subject(s)
Aldehydes/chemistry , Amino Acids/chemistry , Nitro Compounds/chemistry , Quinolizines/chemical synthesis , Decarboxylation , Molecular Structure , Quinolizines/chemistryABSTRACT
Cyclic amines such as 1,2,3,4-tetrahydroisoquinoline undergo regiodivergent annulation reactions with 4-nitrobutyraldehydes. These redox-neutral transformations enable the asymmetric synthesis of highly substituted polycyclic ring systems in just two steps from commercial materials. The utility of this process is illustrated in a rapid synthesis of (-)-protoemetinol. Computational studies provide mechanistic insights and implicate the elimination of acetic acid from an ammonium nitronate intermediate as the rate-determining step.
Subject(s)
Acetates/chemistry , Amines/chemical synthesis , Ammonium Compounds/chemistry , Tetrahydroisoquinolines/chemistry , Aldehydes/chemistry , Amines/chemistry , Catalysis , Molecular Structure , Oxidation-Reduction , Quantum TheoryABSTRACT
Cyclic amines such as pyrrolidine and 1,2,3,4-tetrahydroisoquinoline undergo redox-annulations with α,ß-unsaturated aldehydes and ketones. Carboxylic acid promoted generation of a conjugated azomethine ylide is followed by 6π-electrocylization, and, in some cases, tautomerization. The resulting ring-fused pyrrolines are readily oxidized to the corresponding pyrroles or reduced to pyrrolidines.
Subject(s)
Aldehydes/chemistry , Amines/chemistry , Ketones/chemistry , Amines/chemical synthesis , Azo Compounds/chemistry , Carbon/chemistry , Carboxylic Acids/chemistry , Crystallography, X-Ray , Cyclization , Hydrogen/chemistry , Isoquinolines/chemical synthesis , Isoquinolines/chemistry , Molecular Conformation , Oxidation-Reduction , Pyrrolidines/chemical synthesis , Pyrrolidines/chemistry , Thiosemicarbazones/chemistryABSTRACT
In contrast to the continuously growing number of methods that allow for the efficient α-functionalization of amines, few strategies exist that enable the direct functionalization of amines in the ß-position. A general redox-neutral strategy is outlined for amine ß-functionalization and α,ß-difunctionalization that utilizes enamines generated inâ situ. This concept is demonstrated in the context of preparing polycyclic N,O-acetals from simple 1-(aminomethyl)-ß-naphthols and 2-(aminomethyl)-phenols.
Subject(s)
Amines/chemistry , Cyclization , Oxidation-ReductionABSTRACT
BACKGROUND: This study was conducted to evaluate the occurrence and fate of fetal lumbar rib induced by Scutellariae radix (SR) in rats. METHODS: Water extracts of SR were orally administered to pregnant rats from day 7 to day 17 of gestation at a dose of 186 mg/kg/day, equivalent to 25 g/kg of starting material, representing a 100-fold increase over typical human intake level. RESULTS: The incidence of fetal lumbar rib in the SR-treated group was increased on gestational day 20 and then decreased on postnatal day 50. The weight of fetuses in the SR-treated group tended to be less than that in the control group. Alkaline phosphatase in SR-treated dams was increased on gestational day 20, but was decreased on postnatal day 50. There were no significant differences between the vehicle control and SR-treated groups in maternal body weight, embryological, histopathological, hematological, and serum biochemical changes. CONCLUSIONS: The present data suggest that the appearance of lumbar rib induced by SR is a transient fetal variation rather than teratogenicity or maternal toxicity.
