The synthesis and biological evaluation of d-myo-inositol 1,4,5-trisphosphate receptor ligands
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The intracellular second messenger InsP₃ is a vital molecule in the regulation of Ca²⁺ signalling. Ca²⁺ mediates a wide range of cellular activities from fertilisation and cell differentiation through to apoptoisis. Using X-ray crystal structure data and molecular modelling, a series of novel InsP₃ analogues were designed as selective InsP₃R-antagonists. Two novel synthetic routes have been developed for the synthesis of these analogues. The first route uses a Ferrier-II rearrangement to provide enantiopure inositol intermediates, whereas, the second route employs a diastereomeric resolution to obtain the enantiopure inositols. The successful synthesis of InsP₃ and a series of 5-position modified analogues are reported herein.
Thesis, PhD Doctor of Philosophy
Embargo Date: Electronic version restricted until 11th December 2010 (Restriction now expired. Awaiting final permissions to release full text)
Embargo Reason: Thesis restricted in accordance with University regulations
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