Conformationally defined retinoic acid analogues. 5. Large-scale synthesis and mammary cancer chemopreventive activity for (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30).

Retinoids that activate the nuclear retinoid X receptors (RXRs) display potential for chemoprevention of breast cancer. We previously reported that 9cUAB30 (1) is an RXR-selective retinoid. To explore its in vivo chemopreventive activity, multigram quantities of 1 were needed. Here, we describe a modified synthesis that yields up to 100 g of 1. We further demonstrate that 1 is very effective in the prevention of N-methyl-N-nitrosourea induced mammary cancers in rats without signs of toxicity.