Abstract
The DNA gyrase inhibitor cyclothialidine was shown to be an interesting
lead structure for the search of new antibacterials. During extensive
work elucidating the structure-activity relations, it was demonstrated
that variation of the lactone ring size of its bicyclic core was
tolerated. Indeed, even ‘seco ’ analogues
exhibited DNA gyrase inhibitory activity. These derivatives were
subsequently found to be conveniently accessible by a reductive
thiolation approach. Application of this methodology to cyclic systems established
an alternative, concise, and flexible synthetic access to congeners
of cyclothialidine of varying ring size which so far had been prepared
by Mitsunobu lactonization of the corresponding seco acids.
Key words
cyclothialidine - DNA gyrase inhibitor - antibacterials - reductive thiolation - macrocyclization
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