Novel 2,5-Disubstituted 1,3-Dioxanes and Oxazolidines as Potential Chemoprevention Agents and Building Blocks for Organic Synthesis

2,5-Disubstituted 1,3-dioxacycloalkanes have recently been found to be promising lead compounds that possess potent anti-inflammatory activity and therefore may act as chemo-prevention agents. Encouraged by this we have designed and synthesized a new series of 5-amino-2-heteroaryl-1,3-dioxanes. Starting from N-protected 2-aminopropane-1,3-diol and the corresponding aromatic aldehydes, the products were isolated without isomeric inversion at the deprotection step. This is the first broadly applicable synthetic approach to the acetalization of heteroaromatic aldehydes to give 5-amino-1,3-dioxanes. Our route provides a mild access to both isomers of this kind of dioxane, that is, cis and trans products, as well as 4-(hydroxymethyl)-2-heteroaryloxazolidines, which are useful building blocks in organic synthesis.