Efficient method for introducing vineomycin-fridamycin-type side chain. Total synthesis of fridamycin E

Phytotoxin produced by the netted scab pathogen, Streptomyces turgidiscabies strain 65, isolated in Sweden

“…Genetic analysis of the bacterium in this study showed that the strain belongs to species S. turgidiscabies but that its toxicogenic region in PAI, including the thaxtomin biosynthetis gene cluster, differs from that of S. turgidiscabies which causes deep pitting and other severe scab symptoms. Consistent with these findings, S. turgidiscabies strain 65 did not produce thaxtomin but did produce a newly identified phytotoxin called fridamycin E. Fridamycin E is the aglycone of fridamycin A (= vineomycinone B 2 ) (Matsumoto et al 1991), but there is no report on its biosynthetic pathway or biosynthetic genes.…”

“…1). The absolute stereochemistry of isolated fridamycin E was the same as previously reported (Matsumoto et al 1991) …”

“…Antibiotic activity of fridamycin E against Gram-positive bacteria has been reported (Matsumoto et al 1991), but this is the first report of phytotoxicity associated with fridamycin E.…”

A Chemoenzymatic, Enantioconvergent, Asymmetric Total Synthesis of(R)‐Fridamycin E

“…Finally, a one-pot, multistep oxidation of (R)-5 using KMnO 4 cat./NaIO 4 involving initial deprotection of both MOM-aryl ethers, subsequent oxidation of the anthracene core to form the anthraquinone moiety, and oxidative cleavage of the alkene unit to furnish the carboxylic acid, gave (R)-fridamycin E in 32 % yield. In order to allow spectroscopic characterization of the target compound, (R)-fridamycin E methyl ester (6) = +8.9) [5] revealed its absolute configuration to be identical with that of the natural material. Its physical and spectroscopic data were in good agreement with literature values.…”

“…The unnatural (S)-enantiomer of 1 has been obtained in low yield by a Marschalk reaction of mono-protected 1,5-dihydroxy-9,10-anthraquinone (anthrarufin, 2) with a chiral building block derived from (S)-lactic acid. [4] Subsequently, nucleophilic addition of the anion of a suitably substituted anthracene derivative to an α-chiral aldehyde was reported to give the coupling product in excellent yields; however, elaboration of the chiral β-hydroxycarboxylic acid side-chain required a further nine steps to complete the synthesis of (R)-fridamycin E. [5] A classic approach involving the Ti IV -mediated aldol addition of α-lithiated (-)-menthyl acetate as chiral auxiliary onto an acetonyl-substituted anthrarufin ether suffered similar drawbacks, as the diastereomers thus ob-inversion sequence without formation of the undesiredstereoisomer.…”