Ceramides
with ultralong chains (≥30 carbons), also known
as acylceramides, play a critical role in the survival of mammals
on dry land. An efficient and scalable synthesis of four major classes
of ultralong human skin ceramides is reported. The key approach involves
the use of a succinimidyl ester that acts as a protective group, helps
overcome the extremely low solubility, and simultaneously activates
the fatty acid for its clean and high-yielding attachment to a sphingoid
base