Study On The Total Synthesis Of (±)-4-demethylenglerin A Development Of Efficient Processes For The Preparation Of LXY6006,a Structurally Simplified Analogue Of Saucernetin-8

Racemic4-demethylenglerin A (1), a simplified analogue of the guaiane-type sesquiterpene englerin A, has been synthesized. The cyclic hydrocarbon core structure was built through modified Metz approach using epoxynitrile cyclization and direct Aldol reaction to prepare the precursor of RCM. The primary cytotoxicity test summerized that C4methyl maybe has markedly impacts on the bioactivity. Saucernetin-8, isolation from active root extracts of Saururus cernuus L, has shown potent and selective inhibition on a variety of tumor cells, especially on the hypoxia inducible factor-la (HIF-la). LXY6006was a simplified analogue of Saucernetin-8, and revealed stronger inhibition both on HIF-la and a variety of cancer cells, compared to Saucernetin-8. Furthermore, the molecular architecture of LXY6006is fantastic, possessing six chiral centers. In order to meet the needs of experiments for pharmacology and pharmacokinetic, a modified preparation methods of LXY6006was devolped:1) The side chain has been prepared via Grignard reaction, starting with L-Lactic acid ethyl ester, in quantity;2) The stereoselective reduction of chiral propiophenone was was studyied carefully;3) Separated the LXY6006from its isomers and identified its configuration.