Diazonamide

Nicolaou and co-workers established the severely strained A-ring oxazole (21) in their total synthesis of antitumor agent diazonamide A through initial oxidation of the hindered alcohol of intermediate 20 with TPAP and subsequent Robinson-Gabriel cyclodehydration of the resultant ketoamide with a mixture of POCI3 and pyridine (1 2) at 70°C. ... 

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... 

Scheme 7.14. Domino reduction/nucleophilic cyclization procedure in the synthesis of diazonamide A (7-43).

Recently, synthesis of the 4-arylindole portion of the antitumor agent diazonamide has been achieved starling from 3-bromo-2-methylnitrobenzene via Suzuki coupling and the Batcho reaction.67b... 

The indole bis-oxazole 120, a potential intermediate for the synthesis of the marine natural product diazonamide A, has been synthesised starting from valinamide 116 and... 

Stille couplings also have been exploited in the synthesis of the aromatic macrocyclic core of diazonamide A (2) [5, 20]. Pattenden s group utilized the Pd-catalyzed coupling between the 3-stannyl substituted indole 23 and the 3-bromooxazole 24 to provide a particularly expeditious route to the ring system 25 [20]. In addition, Harran s group secured the connection between bromooxazole 12 and vinylstannane 26 also using a Stille coupling [5]. 

The synthesis of some alcaloids has been achieved by means of the amide version of PFR [201]. Another application is the recent synthesis of diazonamides, an unusual group of alkaloids [202]. In this case, a macrolactam was irradiated. 

Analogous rearrangements have also been performed by both Fu [73] and Vedejs [105] on (9-acyl benzofuranones and (9-acyl oxindoles to provide synthetic intermediates potentially suitable for elaboration to diazonamide A and various oxin-dole-based alkaloids such as gelsemine respectively. Peris has also examined both Fu s and Vedejs chiral 4-DMAP catalysts for effecting diastereoselective carboxyl migrations of 3-arylbenzofuranones [109]. 

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). 

The Pd-catalyzed aryl-alkenyl and alkenyl-aryl coupling reactions involving Zn, A1 and Zr have been applied to the syntheses of a fair number of natural products26. Recent examples published in the last several years include the syntheses of UB-165107 and (—)-diazonamide A108 (Scheme 35). 

One of the more interesting and structurally complex indole-containing peptides is the previously described diazonamide (A and B) from the ascidian Diazona... 

Li J, Jeong S, Esser L, Harran PG (2001) Total Synthesis of Nominal Diazonamides - Part 1 Convergent Preparation of the Structure Proposed for (-)-Diazonamide A. Angew Chem Int Ed 40 4765... 

Ritter T, Carreira EM (2002) The Diazonamides The Plot Thickens. Angew Chem Int Ed 41 2489... 

Nicolaou KC, Chen D Y-K, Huang X, Ling T, Bella M, Snyder SA (2004) Chemistry and Biology of Diazonamide A First Total Synthesis and Confirmation of the True Structure. J Am Chem Soc 126 12888... 

Cruz-Monserrate Z, Vervoort HC, Bai R, Newman DJ, Howell SB, Los G, Mullaney JT, Williams MD, Pettit GR, Fenical W, Hamel E (2003) Diazonamide A and a Synthetic Structural Analog Disruptive Effects on Mitosis and Cellular Microtubules and Analysis of Their Interactions with Tubulin. Mol Pharmacol 63 1273... 

For an auxiliary-controlled, diastereoselective example of the Black rearrangement, aiming at the synthesis of diazonamide A, see Ref. [92]. 

Wipf, P. Methot, J.-L. Synthetic studies toward diazonamide A. A novel approach for polyoxa-zole synthesis. Org. Lett. 2001, 3, 1261-1264. 

Wang G, Shang L, Burgett AWG, Harran PG, Wang X (2007) Diazonamide toxins reveal an unexpected function for ornithine d-amino transferase in mitotic cell division. Proc Natl Acad Sci USA 104 2068-2073... 

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