Synthesis of febrifugine derivatives and a solution to the puzzle of the structural determination of febrifugine

Concise Asymmetric Synthesis of (+)-Febrifugine Utilizingtrans-Selective Intramolecular Conjugate Addition

“…Racemic g-substituted a,b-unsaturated ketones 2a and 2b were prepared from 2-hydroxypiperidines 3a 9 and 3b 7i by Wittig reactions, and 2c was synthesized by protecting 2a (Scheme 2).…”

Enantiodivergent Synthesis of Halofuginone by Candida antarctica Lipase B (CAL-B)-Catalyzed Kinetic Resolution in Cyclopentyl Methyl Ether (CPME)

“…The combined organic layers were washed with brine (40 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude intermediate 9 in 96% yield as a colorless oil, which was used in the next step without further purification. 18 (867 mg, 3.45 mmol) in anhydrous THF (17 mL) was then added and the mixture allowed to warm to room temperature and stirred overnight. Then Et2O (40 mL) was added and the organic layer was washed with a saturated aqueous solution of NH4Cl (2 x 40 mL), brine (40 mL) and dried over Na2SO4.…”

“…In this way we could establish an efficient protocol of possible industrial interest, and also useful to quickly prepare both enantiomers of halofuginone for comparative bioassays. Scheme 1 Previous literature reports on EKR and the present work Thus, commercially available, N-Cbz protected 1,2,3,4tetrahydropyridine 8 (Scheme 2) was treated with OXONE® (2 equiv) in acetone/water and in the presence of K2CO3 (2 equiv) to obtain hemiaminal 9 (96% yield) 18 which, directly as a crude reaction mixture, was subjected to Horner-Wadsworth-Emmons olefination by reaction with phosphonate 10 19 to give alcohol 11 with E geometry. 9 Treatment of crude 11 with BF3•Et2O in anhydrous acetonitrile eventually provided racemic 3a in mixture with furan derivative 12 (15% by 1 H NMR).…”

Febrifugine and Its Analogs: Studies for Their Antimalarial and Other Therapeutic Properties

“…After some years, Baker et al [20] achieved a racemic synthesis of febrifugine. In 2003, Takeuchi et al [25] conducted a synthetic study of febrifugine and solved the puzzle surrounding the stereochemical isomerization of febrifugine. Based on the work of Baker et al, Hill and Edward [22] proposed the absolute configuration 5.…”