Ester dienolate [2,3]-Wittig rearrangement in natural product synthesis: diastereoselective total synthesis of the triester of viridiofungin A, A2, and A4.
[structure: see text] An ester dienolate [2,3]-Wittig rearrangement was utilized to access the alkylated citric acid skeleton 6 that is characteristic for the viridiofungins and other members of the alkyl citrate family of secondary natural products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the rearrangement product (+/-)-syn-16 in moderate yield and with very good diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the viridiofungins. Amide formation between the racemic viridiofungin precursors 35a-c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by preparative reversed-phase HPLC provided the isopropyl dimethyl ester of viridiofungin A ((+)-39a), A2 ((+)-39b), and A4 ((+)-39c) as well as the nonnatural diastereomers (-)-38a-c.
Pollex
Annett
A
Institut für Organische Chemie, Technische Universität Dresden, 01062 Dresden, Germany.
Millet
Agnès
A
Müller
Jana
J
Hiersemann
Martin
M
Abraham
Lars
L
D000466:Alkadienes / Q000737:chemistry*; D001427:Bacterial Toxins / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D002951:Citrates / Q000138:chemical synthesis*; D004952:Esters / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000466:Alkadienes; D001427:Bacterial Toxins; D002951:Citrates; D004952:Esters; C503218:pinnamine; C106753:viridiofungin A; D014443:Tyrosine