Stereoselective Synthesis of 6-Substituted Decahydroisoquinoline-3-carboxylates: Intermediates for the Preparation of Conformationally Constrained Acidic Amino Acids

Article abstract of DOI:10.1021/jo00104a051

In this article we describe the stereoselective preparation of two 6-(hydroxymethyl) substituted decahydroisoquinoline-3-carboxylates, which are useful in the synthesis of a number of excitatory amino acid antagonists, e.g., (-)-1a (LY235959), (-)-2a (LY202157) and (-)-3a (LY293558).For example, the known ketone 4 was converted to either the (3SR,4aRS,6SR,8aRS)-alcohol 18 or the (3SR,4aRS,6RS,8aRS)-alcohol 21, the former via a stereoselective hydroboration reaction, the latter via a stereoselective enol ether hydrolysis followed by reduction.These C-6 epimeric alcohols were easily converted to a number of useful intermediates, e.g., aldehydes, bromides and iodides.If we used resolved keone 4, then these intermediates could be obtained in optically active form.In either racemic or non-racemic form, these intermediates provided access to a number of diastereomerically pure amino acids that were difficult to obtain by earlier routes.