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Total Synthesis of Myxovirescins, 2 Assembly of the “Northwestern” Part [C(15)–C(28)]
Author(s) -
Sefkow Michael,
Neidlein Axel,
Sommerfeld Thimo,
Sternfeld Francine,
Maestro Miguel A.,
Seebach Dieter
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199419940713
Subject(s) - chemistry , stereochemistry
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, 1 H‐ and 13 C‐NMR spectra) and by elemental analysis.