157733-60-3Relevant academic research and scientific papers
Total Synthesis of Myxovirescins, 2. Assembly of the "Northwestern" Part
Sefkow, Michael,Neidlein, Axel,Sommerfeld, Thimo,Sternfeld, Francine,Maestro, Miguel A.,Seebach, Dieter
, p. 719 - 730 (2007/10/02)
The part of the target molecules myxovirescins A and M containing the atoms C(15)-C(28) is described in this paper (for retrosynthetic analysis see Scheme 1).There are three stereogenic centers which are incorporated by using (S)-2-hydroxymethyl-butanoic acid and the appropriate enantiopure diastereoisomeric 2,4-dimethyl-glutaric acids as building blocks (Schemes 2-4).These are joined by the achiral unit 4-oxo-hex-5-enoic acid.The key steps of the assembly are a cuprate Michael addition (Scheme 5) and a nucleophilic addition of a Li derivative to an aldehyde (Scheme 6).In both cases the organometallic reagents are generated by I/Li exchange using two equiv. of tBuLi.The chiral building blocks are prepared by yeast reduction of ethyl 2-formyl-butanoate and by resolution of the 2,4-dimethyl-pentanedioic acid monomethyl ester with phenethylamine; both enantiomers derived from the meso-2,4-dimethyl-glutaric acid are converted to the same aldehyde (5a; "meso-trick", Schemes 3 and 4).The "northwestern" parts for the final synthesis are actually hydroxy sulfones (2 in Scheme 6), the termini of which are ready for Julia coupling and oxidation to a carboxylic acid group.The preparation of the intermediates on gram scales is described and all new compounds are fully characterized by their physical properties, by spectroscopy (IR, 1H- and 13C-NMR spectra) and by elemental analysis. - Key Words: Myxovirescins / Myxococcus virescens / Antibiotics / Macrolides / Lactones / Lactams / Iodine-lithium exchange / Michael additions
