Towards the synthesis of novel protein phosphatase inhibitors
Protein phosphatases (PPases) are important enzymes which mediate dephosphorylation of proteins in eukaryotic cells. These enzymes are involved in a variety of cellular processes, and disruption of their activity has been shown to be involved in the development of diseases such as cancers and Alzheimerâs. Protein phosphatase inhibitors (PPIs) have been used to regulate the activity of these enzymes, and hence, control the development of the cellular processes related to them. However, the lack of potent and selective readily accessible PPIs is a major obstacle to the understanding of these complex biological pathways, and the development of reliable synthetic routes towards new PPIs has therefore generated a significant amount of interest. Several naturally occurring PPIs possess the âADDAâ residue , which has been shown to be crucial for their inhibitory activity. We would like here to report the synthesis of âADDAâ-isoforms such as enantio-ADDA 1 and enantio-iso-ADDA 2 through a convergent approach taking advantage of cross-metathesis methodology, non-aldol aldol and aza-Claisen rearrangements, as well as ÎČ-lactam chemistry. We envisage using our synthetic approaches as a platform to generate
Meiries, Sebastien
QD Chemistry
Towards the synthesis of novel protein phosphatase inhibitors. Protein phosphatases (PPases) are important enzymes which mediate dephosphorylation of proteins in eukaryotic cells. These enzymes are involved in a variety of cellular processes, and disruption of their activity has been shown to be involved in the development of diseases such as cancers and Alzheimerâs. Protein phosphatase inhibitors (PPIs) have been used to regulate the activity of these enzymes, and hence, control the development of the cellular processes related to them. However, the lack of potent and selective readily accessible PPIs is a major obstacle to the understanding of these complex biological pathways, and the development of reliable synthetic routes towards new PPIs has therefore generated a significant amount of interest. Several naturally occurring PPIs possess the âADDAâ residue , which has been shown to be crucial for their inhibitory activity. We would like here to report the synthesis of âADDAâ-isoforms such as enantio-ADDA 1 and enantio-iso-ADDA 2 through a convergent approach taking advantage of cross-metathesis methodology, non-aldol aldol and aza-Claisen rearrangements, as well as ÎČ-lactam chemistry. We envisage using our synthetic approaches as a platform to generate
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