EPC syntheses of trifluorocitronellol and of hexafluoropyrenophorin - A comparison of their physiological properties with the nonfluorinated analogs

The natural products pyrenophorin (1a) and citronellol (2a), in which CH3 g roups are replaced by CF3, were synthesized in enantiomerically pure form f rom simple four-carbon trifluorohydroxy acids (obtained by resolution). The cyclizations of analogous CH3 and CF3 seco acids (cf. 9) to give pyrenopho rin derivatives require different methodologies; the F-6 derivative 10a cou ld be obtained in only very poor yield; in contrast to pyrenophorin. Most s urprisingly, F-6-pyrenophorin (rd) has an extremely poor solubility in comm on organic solvents, and has essentially no antimicrobial activity (see Tab le 2). The synthesis of F-3-citronellol is the first application of an enan tiopure F-3-Roche acid (12) as a synthetic building block (see its derivati ves 17-23). An olfactory comparison of F-3-citronellol [(R)-(+)-2b] with ci tronellol and ent-citronellol (Scheme 6) shows that the fluorine derivative has a "very metallic, aggressive" character and lacks totally the "sweetne ss" of (R)-(+)- and (S)-(-)-2a. A number of generally useful, CF3-substitut ed electrophilic (iodides 4, 18, 37, tosylates 19, 33, aldehydes 5, 29, 39) and nucleophilic (Li dithiane precursor of 5, Li compounds 20, 38) reagent s are described for the first time.