Unexpected behaviour of the reaction between 1,2-diaza-1,3-butadienes and 3-dimethylaminopropenoates: an useful entry to new pyrrolines, pyrroles and oxazolines

We observed a nucleophilic attack by the ene-amino carbon of 3-dimethylaminopropenoates at the terminal carbon of the azo-ene system of 1,2-diaza-1,3-butadienes. In tetrahydrofuran at 65 °C, this attack produced 1-aminopyrrolines with a high degree of cis-stereoselectivity by means of an unusual zwitterionic adduct intermediate followed by intramolecular ring closure. In toluene under reflux, 1-aminopyrrolines produced oxazoline-fused 1-aminopyrrolines. Oxazoline-fused 1-aminopyrrolines were directly obtained by reaction of 1,2-diaza-1,3-butadienes with 3-dimethylaminopropenoates in toluene under reflux. The ring opening of oxazoline-fused 1-aminopyrrolines in acidic or basic media provides highly substituted 1-aminopyrroles. 5-Unsubstituted 1-aminopyrrole derivatives were obtained from 1-aminopyrrolines under basic conditions by loss of dimethylamino and ester groups. We discuss the plausible mechanisms of the ring closure and opening

Divergent Behaviour of the Reactions Between 1,2-Diaza-1,3-dienes and 2,5-Dioxoimidazolidin-4-ylidene-succinates

The different base-promoted regioselective reactions between dialkyl (2E,3E)-2-[(dimethylamino)methylene]-3-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinates and 1,2-diaza-1,3-dienes are investigated. Under the appropriate reaction conditions it is possible to turn the synthesis towards 1,3-dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazoles or 1,3-dioxo-1,2,3,5-tetrahydroimidazo[1,5-a]pyridines. Both these transformations proceed via a double-Michael-addition

SHH Protein Variance in the Limb Bud Is Constrained by Feedback Regulation and Correlates with Altered Digit Patterning

mRNA variance has been proposed to play key roles in normal development, population fitness, adaptability, and disease. While variance in gene expression levels may be beneficial for certain cellular processes, for example in a cell’s ability to respond to external stimuli, variance may be detrimental for the development of some organs. In the bilaterally symmetric vertebrate limb buds, the amount of Sonic Hedgehog (SHH) protein present at specific stages of development is essential to ensure proper patterning of this structure. To our surprise, we found that SHH protein variance is present during the first 10 hr of limb development. The variance is virtually eliminated after the first 10 hr of limb development. By examining mutant animals, we determined that the ability of the limb bud apical ectodermal ridge (AER) to respond to SHH protein was required for reducing SHH variance during limb formation. One consequence of the failure to eliminate variance in SHH protein was the presence of polydactyly and an increase in digit length. These data suggest a potential novel mechanism in which alterations in SHH variance during evolution may have driven changes in limb patterning and digit length

Addition of ortho-Lithiated Aryloxiranes to Enaminones: A Novel Synthesis of Polysubstituted Isochromanes

The reaction of ortho-lithiated aryloxiranes with various enaminones affords straightforwardly new functionalized isochromanes, as a mixture of two epimeric stereoisomers, in reasonable to very good yields (50-90%). The two diastereomers, which show a high structural variability, could be easily separated by column chromatography