Diazonamide fragments

Recently the use of the boron trifluoride catalysed reaction in the synthesis of the oxazolylindole fragment 25 of the natural product diazonamide A has been reported.<96SL609> Thus the BF3-mediated reaction of the indolyl diazoketoester with acetonitrile gave oxazole 25 with simultaneous removal of the Boc-protecting group (Scheme... 

This oxazole synthesis has been used to prepare some important biologically active compounds such as 3-[2-R-l,3-oxazol-5-yl)indoles (370) (R = Me pimpri-nine R = Et pimprinethine R = Pr WS-30581A] and l-Boc-2-chloro-3-(2-methyl-l,3-oxazol-5-yl)indole, a structural fragment of the cytotoxic marine peptide diazonamide A (371). 

Shortly after Harran s structure revision of diazonamide A (47), Nicolaou and coworkers reported the first total synthesis [39]. Retrosynthetically, assembly of fragments 63-67 could lead to diazonamide A through side-chain excision, chlorination, macrolactamization, aminal and oxazole formation, and bis-aryl ring realization (Scheme 10). 

A new modification of the Chan rearrangement proved to be the basis of a versatile and direct strategy for iterative polyoxazole synthesis suitably exploited for the preparation of the indole-bisoxazole fragment of the complex natural product diazonamide A. Indolyloxazole... 

Bagley, M.C., Hind, S.L., and Moody C.J. (2000) Studies towards the synthesis of diazonamide A. Synthesis of the indole bis-oxazole fragment. Tetrahedron Lett., 41, 6897-6900. 

Sperry, J. and Moody, C.J. (2010) Diazonamide studies. A direct synthesis of the indole bis-oxazole fragment from tri- and tetra-peptides using biomimetic oxidative cydizations. Tetrahedron, 66, 6483-6495. 

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