An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)

The oxidation of a borane intermediate by PFC provides a convenient synthesis of 24-ketolanosteryl acetate

An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)

The oxidation of a borane intermediate by PFC provides a convenient synthesis of 24-ketolanosteryl acetate

An Improved Synthesis of 3β-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)

Abstract: The oxidation of a borane intermediate by PFC provides a convenient synthesis of 24-ketolanosteryl acetate

Configurational Reassignment and Improved Preparation of the Competitive IL-6 Receptor Antagonist 20<i>R</i>,21<i>R</i>-Epoxyresibufogenin-3-formate

20<i>R</i>,21<i>R</i>-Epoxyresibufogenin-3-formate (<b>1</b>) and 20<i>S</i>,21<i>S</i>-epoxyresibufogenin-3-formate (<b>2</b>) were synthesized from commercial resibufogenin (<b>3</b>) using known procedures. The major product (<b>1</b>) was dextrorotatory, as was the major product from the reported synthesis of epoxyresibufogenin-3-formate; however, the literature (+)-compound was assigned the 20<i>S</i>,21<i>S</i>-configuration on the basis of NMR data. We have now unequivocally determined, using single-crystal X-ray structure analyses of the major and minor products of the synthesis and of their derivatives, that the major product from the synthesis was (+)-20<i>R</i>,21<i>R</i>-epoxyresibufogenin-3-formate (<b>1</b>). Our minor synthetic product was determined to have the (−)-20<i>S</i>,21<i>S</i>-configuration (<b>2</b>). The (+)-20<i>R</i>,21<i>R</i>-compound <b>1</b> has been found to have high affinity for the IL-6 receptor and to act as an IL-6 antagonist. A greatly improved synthesis of <b>1</b> was achieved through oxidation of preformed resibufogenin-3-formate. This has enabled us to prepare, from the very expensive commercial resibufogenin, considerably larger quantities of <b>1</b>, the only known nonpeptide small-molecule IL-6 antagonist