ABSTRACT
3-Acyltetramic acids derived from ß-hydroxytyrosine are synthetically challenging. The first route to this structural motif, based upon a condensation between a Meldrum's acid conjugate bearing the acyl side chain, and a ß-hydroxytyrosinate, N-protected by an ortho-nitrobenzyl group is presented. This group enables the Dieckmann cyclization of the resulting N-(ß-ketoacyl)amino ester, after which it can be removed photolytically without compromising the delicate 3'-hydroxy group. This strategy was applied to the first total synthesis of the fungal metabolite F-14329 (1).
Subject(s)
Fungi/metabolism , Pyrrolidinones/chemistry , Tenuazonic Acid/analogs & derivatives , Biological Products/chemical synthesis , Biological Products/chemistry , Cyclization , Paecilomyces/metabolism , Pyrrolidinones/chemical synthesis , Stereoisomerism , Tenuazonic Acid/chemical synthesis , Tenuazonic Acid/chemistryABSTRACT
The second total synthesis of macrocidin A afforded the bioherbicidal fungal metabolite in 16 steps starting from doubly protected l-tyrosine. The 3-octanoyl side chain with the α-methyl group and an ω-bromo epoxide already in place was attached to the tetramic acid via a Yoshii-Yoda acylation, and the macrocycle was eventually closed in 55% yield by a Williamson etherification between the phenolate and the epoxy bromide.
Subject(s)
Ascomycota/chemistry , Pyrrolidinones/chemical synthesis , Ascomycota/metabolism , Molecular Structure , Pyrrolidinones/chemistry , Pyrrolidinones/metabolism , StereoisomerismABSTRACT
A cis-2-aminomethyl-5-phenylpyrrolidine, which is easily available from methyl Boc-L-pyroglutamate, was found to be a highly efficient chiral ligand for Cu(II)-catalysed Henry reactions. Excellent yields (>90%) and superb levels of enantiocontrol (98.5-99.6% ee) were reached with aromatic, heteroaromatic, vinylic, and aliphatic aldehydes (36 examples).
