9-cis tritium-labeled retinoids and intermediates, methods for their synthesis and methods for their use in discovering retinoid X receptor ligands

A method for producing a 9-cis monotritium-labeled retinoid comprising:

• (a) reducing an alkyl ester of the formula:
• ##STR3## with a substantially carrier-free metallo tritide selected from the group consisting of substantially carrier-free lithium aluminum tritide and substantially carrier-free lithium triethyl aluminum tritide to form a ditritium alcohol of the formula:
• ##STR4## (b) oxidizing the ditritium alcohol to a monotritium aldehyde in the presence of an oxidizing agent;
• (c) condensing the monotritum aldehyde with a carbanion equivalent formed by the addition of a base to a phosphonate or phosphine salt of the formula:
• ##STR5## to form a reaction product comprising a mixture of 9-cis monotritium-labeled retinoid ester stereoisomers having the general formula:
• ##STR6## wherein R.sup.1, R.sup.2 and R.sup.3 each independently represent hydrogen or a lower straight chain or branched alkyl having 1-6 carbon atoms;
• R.sup.4 represents hydrogen or a lower straight chain or branched alkyl having 1-12 carbon atoms;
• R.sup.5 represents a lower alkyl having 1-5 carbon atoms;
• R.sup.6 represents hydrogen or a lower straight chain or branched alkyl having 1-12 carbon atoms;
• R.sup.7 represents a lower alkyl having 1-5 carbon atoms;
• R.sup.8 represents hydrogen or a pharmaceutically acceptable salt;
• PX represents dialkyl phosphonate or a triphenyl phosphine salt;
• and the dashed lines in the structures between carbons 11-12 and 13-14 depict olefin bonds that can be in either the trans or cis configuration and further wherein, said 9-cis monotritium-labeled retinoid ester steroisomers display a specific activity of at least 15 Curries per millimole.