I Ceric ammonium nitrate-mediated oxidative cleavages of hemiacetals II Synthesis of beta-proline derivatives through the tandem chain extension-imine capture reaction

A novel ceric ammonium nitrate-mediated oxidative cleavage of hemiacetals generated through the use of the zinc carbenoid-mediated tandem chain extension-aldol reaction was developed. This chemistry has been applied towards the formation of a class of natural products, phaseolinic acids, in two steps from a commercially available beta-keto ester, methyl 4-methoxyacetoacetate. The tandem chain extension-imine capture reaction has also been developed to provide access to beta-proline derivatives. Two activated imines were studied and provided access to different diastereomers, making the chemistry versatile. beta-Keto esters, beta-keto amides, and beta-keto imides were subjected to the tandem chain extension-imine capture reaction conditions and proved to be reasonably successful in most cases. beta-Keto esters were efficient in the synthesis of free --NH beta-proline derivatives in three steps and beta-keto imides were efficient in the synthesis of Boc-protected beta-proline derivatives in just two steps. The zinc carbenoid-mediated chain extension imine capture reaction has developed into a flexible route in obtaining different diastereomers of protected and unprotected beta-proline derivatives in minimal steps from commercially available starting materials

Tandem Chain Extension-Mannich Reaction: An Approach to β-Proline Derivatives

A zinc carbenoid-initiated chain extension reaction provides access to an organometallic intermediate, which can be used to capture activated imines. Deprotection of the nitrogen and reduction provides access to racemic derivatives of β-proline. The relative stereochemistry of the β-proline can be controlled through use of different activating groups on the imine nitrogen

Large recurrent microdeletions associated with schizophrenia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldReduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia