Synthesis of Fluorinated Sphinganine and Dihydroceramide Analogues

With the aim of uncovering inhibitors of dihydroceramide desaturase and ceramide synthase and studying their substrate specificity, the synthesis of short-chain 3-fluorosphinganine and 3-fluorodihydroceramide analogues was effected. The synthesis starts from the known alkynols 1 and 10, respectively, and from the Garner aldehyde 15. The key step is the introduction of a fluorine atom using diethylaminosulfur trifluoride, which proceeds efficiently for erythro-alcohols 2 and 16, but gives rise to cyclization reactions for threo compounds 11 and 17.