Diazonamide macrocycle

Magnus, P., Lescop, C. Photo-Fries rearrangement for the synthesis of the diazonamide macrocycle. Tetrahedron Lett. 2001, 42, 7193-7196. 

Furthermore, the use of light has also been used, wherein Magnus was able to effect the rearrangement and develop a photo-Fries rearrangement for the synthesis of the diazonamide macrocycle (160 161) [80]. Irradiation of 160 in benzene (0.001 M) with a medium pressure mercury vapor lamp at 23°C gave 161 (39%) along with about 20% of the para-isomer. 

Photo-Fries used in the synthesis of the diazonamide macrocycle... 

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]. 

In 2003, Nicolaou reported a synthesis of diazonamide A that utilised a Sml2-mediated heteropinacol coupling to construct the 12-membered macrocyclic... 

Research in the laboratory of P. Magnus showed that the macrocyclic skeleton of diazonamide could be synthesized with the use of macroiactonization followed by a photo-Fries rearrangement. First, the aromatic carboxylic acid and the phenol were coupled with EDCI to form the macrolactone (phenolic ester), which was then exposed to light at high-dilution to cleanly afford the macrocyclic ortho-acylated phenol skeleton of diazonamide. 

Diazonamide A is a potently antimitotic natural product and its penultimate step involves the coupling of macrocyclic amine 104 with (5)-a-hydroxy isovaleric acid and DEPC in 90% yield.46-41... 

In summary, the obvious difference between the two Nicolaou syntheses is the reversed order of the construction of the daunting macrocyclic domains of diazonamide A (47). The initial synthesis installed the macrolactam ring first, followed by photoinduced HBr eUmination for the heterocyclic 12-membered ring. The subsequent synthesis constiucted the heterocyclic core first, which featured a... 

For the total synthesis of macrocyclic compound diazonamide A , Harran s group tried intramolecular HR of highly functionalized iodide 268, although they found the proposed structure to be wrong. Selective endo cyclization took place to give the macrocycle 269 in 82% yield when Pd2(dba)3, AgjCOs, and biphenylyl-... 

Carbopalladation reactions have been shown to be effective in closing macrocyclic rings both in solution and on substrates attached to a solid supportJ In an effort directed toward the synthesis of the cytotoxic natural product diazonamide A 164 a 13-membered ring was assembled (Scheme Palladium-mediated Vi-endo macrocychzation of... 

Scheme 10. Completion of the second macrocyclic subunit of diazonamide A synthesis of advanced intermediate 25.

With both macrocycles successfully generated through the formation of 25, the completion of the target now required only a few finishing touches, the most notable being the installation of the two missing aryl chlorine substituents and the formation of the FH aminal system of diazonamide A (see Scheme 11). The first of... 

Scheme 15. Completion of the heterocyclic subunit of diazonamide A through a hetero-pinacol macrocyclization sequence synthesis of intermediate 44.

Jeong, S., Chen, X. and Harran, P.G. (1998) Macrocyclic triarylethylenes via Heck endocy-clization a system relevant to diazonamide synthesis. J. Org. Chem., 63,8640-1. 

During the course of synthetic study of diazonamide, Harran and coworkers [34] reported an interesting example of Mizoroki-Heck macrocyclization of 83 driven by a phenolic hydroxy group (Figure 7.26). Use of the corresponding methyl ether results in a marked... 

Very recently, MacMillan et al. applied an intermolecular combined Friedel-Crafts-type conjugate addition/cyclization procedure as a key step in the total synthesis of diazonamide A (297) (271). Diazonamides are secondary metabolites isolated from the marine ascidian Diazona sp. (272, 273). Diazonamide A (297) was found to be a potent antimitotic member of this structurally unique family, exhibiting low nanomolar G/50 values towards different human cancer cell lines (272, 274). The unique structure of two 12-membered macrocycles that are conjoined through a triaryl-substituted quaternary stereogenic center (C-10) that is embedded in a furanoindoline core makes this compound a very interesting and... 

The PFR has also been used as a key step in the synthesis of more complex natural products or biologically active compounds, such as capiUarol [165], bikaverin [166, 167], adriamycin [168, 169], rutaretin methyl ether [170], arizonine and caseadine [171 ], diazonamide [172], and Strychnos andAspidosperma alkaloids [173]. Amore recent example is the elegant synthesis of (-)-kendomy cin involving the intramolecular PFR of a macrocyclic lactone (Scheme 31.17) [174,175]. 

Vedejs, E. and Zajac, M.A. (2001) Synthesis of the diazonamide A macrocyclic core via a Dieckmann-type cydisation. Org. Lett., 3, 2451-2454. 

Lachia, M. and Moody, C.J. (2008) The synthetic challenge of diazonamide A, a macrocyclic indole bis-oxazole marine natural product. Nat. Prod. Rep., 25, 227-253. 

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