Development of novel Gemini-cholesterol analogues for retinoid-related orphan receptors

Abstract

Retinoic-acid-related Orphan Receptors (RORs) regulate maintenance of the circadian rhythm and immune response among others and are involved in increasing number of pathologies including autoimmune diseases, cancer and neurological disorders...

Cyclopropylcarbinyl cation chemistry in synthetic method development and natural product synthesis: cyclopropane formation and skeletal rearrangement

“…61 The synthesis began with the C19-hydroxylation of 133 to prepare the known alcohol 117 54 in a four-step sequence, including the two-step isomerization to cyclopropylcarbinol 134 , C6-hydroxy-directed C19 etherification, and BF 3 -mediated cyclopropane ring opening to release the C5–C6 olefin. It should be noted that the transformation from 133 to 134 , which simultaneously protected the C3 alcohol and the C5–C6 olefin, 62 represents a classic example of interconversion of Δ 5 -3β- and 3α,5α-cyclo-6-substituted steroids, 63,64 which involves the intermediacy of a cyclopropylcarbinyl cation (Scheme 18B). With 117 in hand, phosphorylation of the C19-alcohol followed by Confalone's sulfoxide-mediated protocol 65 generated the C7–C8 olefin 138 , which readily underwent homoallylic cyclization to give the 90b -type cyclopropylcarbinyl cation 139 .…”