Studies in the Total Synthesis of (-)-Cassine

2,6-Disubstituted piperidin-3-ol alkaloids constitute an important class of compounds widely found in nature and with interesting biological properties.1 Due to its antimicrobial and anti-inflammatory activities,2 (-)-Cassine has been shown as an important representative of this class of alkaloids and an interesting synthetic target.3 Inspired by the total synthesis of (-)-1-Deoxyaltonojirimycin and (+)-1-Deoxymannonojirimycin developed by our group in 2016,4 we began the total synthesis of (-)-Cassine by the alkylation reaction of our Horner-Wadsworth-Emmons olefination reagent, using iodomethane and LDA in THF. The Horner-Wadsworth-Emmons reaction between the diazophosphonate and N-Cbz-O-TBDPS-serinal furnished the Z-unsatured diazoketone in 59% yield. For the cyclization step, we obtained the NH-insertion product as a single cis-diastereoisomer after exposure to Cu(acac)2. The Luche reduction provided only the cis allylic alcohol as depicted in the scheme below. For the next step, the protection of the hydroxyl group with p-nitro benzoyl chloride is under investigation.