Dihydroceramide Desaturase Inhibition by a Cyclopropanated Dihydroceramide Analog in Cultured Keratinocytes

Scheme 2

Reagents and conditions: (a) Ph₃PCH₃Br, KHMDS, THF, −78°C then rt, 2 h (86%); (b) mCPBA, 0.5 M NaHCO₃, CH₂Cl₂, 0°C then rt, 18 h (42%, erythro:threo = 2.8 : 1); (c) 1-octyne, n-BuLi, BF₃ × Et₂O, THF, −78°C, 30 min (86%); (d) 1 N HCl, THF, 70°C, 18 h (91%); (e) LiAlH₄, DME, 90°C, 12 h (73%); (f) H₂₃C₁₁COCl, NEt₃, MeOH, 0°C then rt, 18 h (65%); (g) Et₂Zn, CH₂I₂, CH₂Cl₂, rt, 24 h (24%).