Synthesis and determination of the absolute configuration of fugomycin and desoxyfugomycin: CD spectroscopy and fungicidal activity of butenolides.
The dibromoalkenes (S)-3 and (R)- and (S)-4 are intermediates in the syntheses of the naturally occurring fungicidal butenolides fugomycin (1) and desoxyfugomycin (2), respectively. The stereoselective bromine-lithium exchange that leads to the carbenoid 12 and the vinyllithium reagent 17 a on the one hand, and palladium-catalyzed coupling reactions of the dibromoalkene 3 and the bromolactone 22 on the other are key steps en route to the butenolides 1 and 2. The chiral building blocks (S)-3, (R)-4, and (S)-4 are readily available from (R)-isopropylideneglyceraldehyde 5, isobutyl (R)-lactate 6 a, and ethyl (S)-lactate 6 b, respectively. The synthetic procedure adopted here permits the absolute configuration of the natural products fugomycin (1) and desoxyfugomycin (2) to be assigned by comparison of their chiroptical properties with those of the synthetic products. The CD spectra of the bromolactone 22, calculated by two different density functional methods (TDDFT, DFT/MRCI), are found to be in good agreement with the measured spectra. On the basis of these calculations, the two CD bands observed could be assigned to n-pi* and pi-pi* transitions, respectively. Fugomycin (1) and the synthetic butenolide 20 displayed high fungicidal activity against botrytis in greenhouse experiments, whereas the saturated lactone 21 was practically inactive.
Braun
Manfred
M
Institut für Organische Chemie und Makromolekulare Chemie, Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany. braunm@uni-duesseldorf.de
Hohmann
Andreas
A
Rahematpura
Jaykumar
J
Bühne
Corinna
C
Grimme
Stefan
S
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020171:Botrytis / Q000187:drug effects; D002942:Circular Dichroism; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure
D000475:Alkenes; D000935:Antifungal Agents; D007783:Lactones; C506629:desoxyfugomycin; C506628:fugomycin; C004511:butenolide; D015107:4-Butyrolactone