Bastadin-6, synthesis

Bis-4-arylidene-5(4//)-oxazolones are easily obtained from aromatic dialdehydes by the Erlenmeyer synthesis. Such bis(oxazolones) react with a,co-diamines to provide a convenient approach to macrolactams.Tandem Erlenmeyer condensation-macrolactamization (TECM) has been used to prepare analogues of naturally occurring, biologically active cyclic peptides such as bastadin-5. 

Kotoku N, Tsujita H, Hiramatsu A, Mori C, Koizumi N, Kobayashi M (2005) Efficient Total Synthesis of Bastadin 6, an Anti-Angiogenic Brominated Tyrosine-Derived Metabolite from Marine Sponge. Tetrahedron 61 7211... 

Scheme 9.12 Kobayashi and coworkers total synthesis of bastadin 6 [144],...

Yamamura and coworkers have used a thallium trifluoroacetate mediated oxidative cyclization in their synthesis of aerothionin and related products and also in the synthesis of bastadin-6, a 28-membered ring lactone. 

SCHEME 164. Synthesis of bastadin-6 using TTN-mediated oxidation as a key step... 

Bamberger rearrangement 419, 801 Basicity, gas-phase 5, 261 Bastadin-6, synthesis of 1315, 1319 BatzeUines 1337 BE-10988 1306 Benzaldehydes—see also Fluorobenzaldehydes, Hydroxybenzaldehydes oxidation of 419, 420, 422, 423 Benzamides—see 2-Hydroxybenzamide Benzanilides—see 2-HydroxybenzaniUde Benzannulation, in synthesis of phenols 450-459... 

An efficient method for the conversion of iV>alkyl-lactams into the corresponding thiolactams, involving treatment with R3O+BF4- followed by NaSH, is reported. Twenty-four-membered macrocyclic amides containing phenylalanine and leucine units have been obtained. A total synthesis of the natural product bastadin-6, which has a 28-membered lactam ring, has been described, and total syntheses of ( )-maysine and ( >ma5dansinol are reported. ... 

Nishiyama, S, and Yamamura, S, (1982) Total synthesis of bastadins. Tetrahedron Lett., 23, 1281-1284. 

Couladouros, E.A. and Moutsos, V.l. (1999) A general synthetic route towards bastadins. Part 1 synthesis of the eastern part of bastadins 4-16. Tetrahedron Lett., 40, 7023-7026. 

Bailey, K.L. and Molinski, T.F, (2002) Synthesis of bastadin analogs through an SNAr coupling strategy. Tetrahedron Lett., 43,9657-9661. 

Couladouros, E.A., Moutsos, V.I., and Pitsinos, E.N. (2003) Synthesis of o-brominated diaryl ethers using symmetrical iodonium salts application to the synthesis of bastadin precursors. ARKIVOC, 92-101. 

Kotoku, N., Tsujita, H., Hiramatsu, A., Mori, C Koizumi, N and Kobayashi, M. (2005) Efficient total synthesis of bastadin 6, an anti-angiogenic brominated tyrosine-derived metabolite from marine sponge. Tetrahedron, 61, 7211—7218. 

The diverse and unique chemical structures, and the variety of biological activities of bromotyrosine derivatives, make them ideal synthetic targets for synthetic and natural products chemists. Studies on the synthesis of bromotyrosine can be traced back to 1912 (194). In former studies, degradation, chemical transformation to known compoimds, or even total synthesis were conducted for the purpose of verifying the structures. Later studies were focused on the total synthesis of more complex structures, such as the spirocyclohexadienylisoxazoline and bastadin ring systems. 

Guo et al. developed a chemoenzymatic strategy for the synthesis of bastadins-2, -3, and -6 (232). The requisite dimeric dityrosine and isodityrosine were successfully prepared by C-C and C-O oxidative phenolic coupling of mono- and dihalogenated derivatives of tyrosine and tyramine using horseradish (233) and soybean peroxidases. 

Couladouros and Moutsos reported a general synthetic route for the synthesis of the eastern and western parts of bastadins, which can be used for construction of bastadins 4—16 (234-236). The brominated biaryl ethers are synthesized using the iodonium salt method. The eastern segment 352 was synthesized within 18 steps in 15.5% overall yield. The western segment 353 and 354, which can be used to construct bastadins-8 (212), -10 (214), -12 (216), and -17 (221), was synthesized in 13 steps (see the following scheme). 

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