A Concise Total Synthesis of the Non-peptide Bradykinin B1 Receptor Antagonist Velutinol A

A concise route to the bradykinin B1 receptor antagonist velutinol A, a natural product isolated from the rhizomatous of mandevilla velutina (Apocynaceae), has been developed. This synthesis features the highly regioselective construction of Δ14 silyl enol ether 13 from diol 8a followed by stereoselective introduction of a sterically hindered β‐hydroxy group at the C14 position by Rubottom oxidation. A prolonged reaction time and the presence of an excess amount of mCPBA during this step allowed the double Rubottom oxidation to proceed through intermediate 16 to install β‐hydroxy groups at the C14 and C16 positions in one pot. The following conversions from α‐keto‐diol 18 to the target natural product were accomplished by reduction of the ketone at C15, oxidative cleavage of the C15–16 bond, and subsequent deprotection and intramolecular acetalization. Made it! A concise route to the bradykinin B1 receptor antagonist velutinol A, a natural product isolated from the rhizomatous of mandevilla velutina (Apocynaceae), has been developed. The key step in the synthesis is the double Rubottom oxidation for the selective introduction of β‐hydroxy groups at the C14 and C16 positions.