A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• conversion to the appropriate intermediates and subsequent acylation with lauric acid furnished the target compound. Keywords: AD mix-β; [bmim][PF6]; DDQ; HPA-12; lipase; Introduction Ceramides belong to the family of sphingolipids (SLs) and are synthesized de-novo in the endoplasmic reticulum (ER) [1

• (HPA-12, 1, Figure 1) as the first inhibitor of CERT-mediated ceramide transport [11]. However, the initially determined (1R,3R) configuration of the most active HPA-12 stereoisomer (compound 1, Figure 1) was later revised to (1R,3S) configuration (compound 2, Figure 1) by Berkeš et al. in 2011 [12

• ]. Since then, HPA-12 has been the subject of extensive biological evaluation. The HPA-12-mediated CERT knockdown has been associated with restoration of cell death in paclitaxel-resistant ovarian cancer cells [3] and also with the increased rate of ceramide-induced apoptosis following UVB irradiation