Premium
EPC Syntheses of Trifluorocitronellol and of Hexafluoropyrenophorin – A Comparison of Their Physiological Properties with the Nonfluorinated Analogs
Author(s) -
Götzö Stephan P.,
Seebach Dieter,
Sanglier JeanJacques
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199910)1999:10<2533::aid-ejoc2533>3.0.co;2-o
Subject(s) - citronellol , chemistry , enantiopure drug , organic chemistry , electrophile , nucleophile , derivative (finance) , yield (engineering) , stereochemistry , combinatorial chemistry , enantioselective synthesis , geraniol , essential oil , catalysis , chromatography , financial economics , economics , materials science , metallurgy
The natural products pyrenophorin ( 1a ) and citronellol ( 2a ), in which CH 3 groups are replaced by CF 3 , were synthesized in enantiomerically pure form from simple four‐carbon trifluorohydroxy acids (obtained by resolution). The cyclizations of analogous CH 3 and CF 3 seco acids (cf. 9 ) to give pyrenophorin derivatives require different methodologies; the F 6 derivative 10a could be obtained in only very poor yield; in contrast to pyrenophorin. Most surprisingly, F 6 ‐pyrenophorin ( 1d ) has an extremely poor solubility in common organic solvents, and has essentially no antimicrobial activity (see Table 2). The synthesis of F 3 ‐citronellol is the first application of an enantiopure F 3 ‐Roche acid ( 12 ) as a synthetic builiding block (see its derivatives 17–23 ). An olfactory comparison of F 3 ‐citronellol [( R )‐(+)‐ 2b ] with citronellol and ent ‐citronellol (Scheme 6) shows that the fluorine derivative has a “very metallic, aggressive” character and lacks totally the “sweetness” of ( R )‐(+)‐ and ( S )‐(–)‐ 2a . A number of generally useful, CF 3 ‐substituted electrophilic (iodides 4 , 18 , 37 , tosylates 19 , 33 , aldehydes 5 , 29 , 39 ) and nucleophilic (Li dithiane precursor of 5 , Li compounds 20 , 38 ) reagents are described for the first time.