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Total Synthesis of Disciformycin A and B: Unusually Exigent Targets of Biological Significance
Author(s) -
Kwon Yonghoon,
Schulthoff Saskia,
Dao Quang Minh,
Wirtz Conny,
Fürstner Alois
Publication year - 2018
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.201705550
Subject(s) - silylation , total synthesis , residue (chemistry) , cleave , chemistry , protecting group , stereochemistry , isomerization , metathesis , ring (chemistry) , alkyne , combinatorial chemistry , organic chemistry , enzyme , catalysis , alkyl , polymer , polymerization
The first total synthesis of the potent antibiotic disciformycin B ( 2 ) is described, which is exceptionally isomerization‐prone and transforms into disciformycin A ( 1 ) even under notably mild conditions. To outweigh this bias, the approach to 2 hinged on the use of a silyl residue at C4 to lock the critical double bond in place and hence insure the integrity of the synthetic intermediates en route to 2 . This tactic was instrumental for the preparation of the building blocks and formation of the macrocyclic ring via ring closing alkyne metathesis (RCAM). To make the end game successful, however, it proved necessary to cleave the C‐silyl protecting group off; it was at this stage that the exceptional sensitivity of the target became fully apparent.