3398-48-9Relevant articles and documents
Total synthesis of the antitumor antibiotic (±)-streptonigrin: First- and second-generation routes for de novo pyridine formation using ring-closing metathesis
Donohoe, Timothy J.,Jones, Christopher R.,Kornahrens, Anne F.,Barbosa, Luiz C. A.,Walport, Louise J.,Tatton, Matthew R.,O'Hagan, Michael,Rathi, Akshat H.,Baker, David B.
, p. 12338 - 12350 (2014/01/17)
The total synthesis of (±)-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing (±)-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric Suzuki-Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time.
Determination of the absolute configuration of the chiral biaryl system in the streptonigrin antibiotics by exciton coupled circular dichroic spectroscopy
Tennant, Shaun,Rickards, Rodney W.
, p. 15101 - 15114 (2007/10/03)
The absolute configuration of the chiral phenylpyridyl segment of the Actinomycete antibiotic streptonigrin (1) is defined as R by analysis of the exciton coupled circular dichroic spectra of selected derivatives, The absolute configuration of the co-occurring 10'-O-demethylstreptonigrin (2) is assigned as R by chiroptical correlation with streptonigrin. Circular dichroic spectroscopy indicates that the related phenylpyridone streptonigrone (5) is either achiral or a racemate.
