STEREOSELECTIVE SYNTHESIS OF 6-SUBSTITUTED DECAHYDROISOQUINOLINE-3-CARBOXYLATES - INTERMEDIATES FOR THE PREPARATION OF CONFORMATIONALLY CONSTRAINED ACIDIC AMINO-ACIDS

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 anta gonists, e.g., (-)-1a (LY235959), (-)-2a (LY202157) and (-)-3a(LY29355 8). For example, the known ketone 4 was converted to either the (3SR,4 aRS,6SR,8aRS)-alcohol 18 or the (3SR,4aRS,6RS,8aRS)-alcohol 21, the fo rmer via a stereoselective hydroboration reaction, the latter via a st ereoselective enol ether hydrolysis followed by reduction. These C-6 e pimeric alcohols were easily converted to a number of useful intermedi ates, e.g., aldehydes, bromides and iodides. If we used resolved keton e 4, then these intermediates could be obtained in optically active fo rm. In either racemic or non-racemic form, these intermediates provide d access to a number of diastereomerically pure amino acids that were difficult to obtain by earlier routes.