Novel Synthetic Access to 24a-Homochol-5-en-24a-oate Scaffold from Stigmasterol

we have developed a four-step, high-yield and multi-gram scale synthetic route giving access to the scaffold of 24a-homochol-5-en-24a-oate starting from stigmasterol, a common and inexpensive phytosterol. Differently from previous approaches, the synthetic route herein reported is the first one which furnishes the desired scaffold endowed with the masked/protected 3b-hydroxy-5,6-ene moiety in the steroid body. This feature could be extremely useful in those cases in which the presence of the double bond would be incompatible with the further manipulation of the intermediate. The straightforward unmasking of the 6b-methoxy-3a,5-cyclo moiety to give the original 3b-hydroxy-5,6-ene function by mild acidic conditions supports the practical utility of our synthetic strategy. In our hands 22 has shown to be a valid intermediate towards the preparation of novel LXR modulators whose synthesis and biological profile will be duly reported.