Premium
Total Synthesis of Branimycin: An Evolutionary Approach
Author(s) -
Enev Valentin S.,
Felzmann Wolfgang,
Gromov Alexey,
Marchart Stefan,
Mulzer Johann
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201200257
Subject(s) - desymmetrization , polyketide , total synthesis , side chain , ketone , stereochemistry , chemistry , carbon chain , enantioselective synthesis , combinatorial chemistry , organic chemistry , catalysis , biosynthesis , enzyme , polymer
The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis ‐dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring‐closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107 , to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization.