Bastadin

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. 

Franklin, M.A. Penn, S.G. Lebrilla, C.B. Lam, T.H. Pessah, I.N. Molinski, T.F. (1996) Bastadin 20 and bastadin O-sulfate esters from lanthella basta novel modulators of the RyiR FKBP12 rec tor complex. J.Nat. Prod., 59,1121-7. 

Tyrosine-derived metabolites in this section do not include spiro-cyclohexadienyl-isoxazolines and related compounds (Sect. 3.22.3.3) or bastadins (Sect. 3.22.3.4), but they do include tyrosine-derived alkaloids that were covered in the Alkaloids section in the first survey (1). The prolific bryozoan Amathia convoluta, collected in Tasmania, has yielded amathamide G (1953) (1814), the latest of several amath-amide alkaloids from the genus Amathia (1). A Florida collection of this animal furnished the new convolutamines A-E (1954—1958) (1815), F (1959), and G (1960) (1425), and a Tasmanian sample of this bryozoan afforded convolutamine H (1961) (1319). A study of Amathia convoluta from the North Carolina coast has yielded volutamides A-E (1962-1966) (1816). Volutamides B and C reduce feeding by the pinfish (Lagodon rhomboids) and the urchin (Arbacia punctulata), respectively, and volutamides B and D are toxic toward larvae of the hydroid Eudendrium carneum. The New Zealand Amathia wilsoni contains the six novel amathaspiramides A-F (1967-1972) (1817). 

Fig. 3.30 Ianthella basta, a sponge rich in the bastadins 2053-2061 (Photo F. J. Schmitz)...

A Guam specimen of Ianthella basta has afforded the novel 34-O-sulfatobasta-din-9 (2127) (1855), and the sponge Dendrilla cactos from India has yielded bastadins-22 (2128) and -23 (2129) (1899). 

These novel tetrameric bromotyrosine metabolites display a range of biological activities, including effects on calcium channels (1900), lipoxygenase inhibition (1772), tumor angiogenesis inhibition (1901), and endothelial cell anti-proliferation (1902). Syntheses of several bastadins have been accomplished (1903,1904). 

Pettit GR, Butler MS, Bass CG, DoubekDL, Williams MD, Schmidt JM, Pettit RK, Hooper JNA, Tackett LP, Filiatrault MJ (1995) Antineoplastic Agents, 326. The Stereochemistry of Bastadins 8, 10, and 12 from the Bismark Archipelago Marine Sponge Ianthella basta. J Nat Prod 58 680... 

Franklin MA, Penn SG, Lebrilla CB, Lam TH, Pessah IN, Molinski TF (1996) Bastadin 20 and Bastadin O-Sulfate Esters from Ianthella basta Novel Modulators of the RyiR FKBP12 Receptor Complex. J Nat Prod 59 1121... 

Coll JC, Kearns PS, Rideout JA, Sandar V (2002) Bastadin 21, a Novel Isobastarane Metabolite from the Great Barrier Reef Marine Sponge Ianthella quadrangulata. J Nat Prod 65 753... 

Reddy AV, Ravinder K, Narasimhulu M, Sridevi A, Satyanarayana N, Kondapi AK, Venkateswarlu Y (2006) New Anticancer Bastadin Alkaloids from the Sponge Dendrilla cactos. Bioorg Med Chem 14 4452... 

Masuno MN, Pessah EM, Olmstead MM, Molinski TF (2006) Simplified Cyclic Analogues of Bastadin-5. Structure-Activity Relationships for Modulation of the RyRl/FKBP12 Ca+2 Channel Complex. J Med Chem 49 4497... 

Aoki S, Cho S, Ono M, Kuwano T, Nakao S, Kuwano M, Nakagawa S, Gao J-Q, MayumiT, Shibuya M, Kobayashi M (2006) Bastadin 6, a Spongean Brominated Tyrosine Derivative, Inhibits Tumor Angiogenesis by Inducing Selective Apoptosis to Endothelial Cells. Anti-Cancer Drugs 17 269... 

Aoki S, Cho S, Hiramatsu A, Kotoku N, Kobayashi M (2006) Bastadins, Cyclic Tetramers of Brominated-Tyrosine Derivatives, Selectively Inhibit the Proliferation of Endothelial Cells. J Nat Med 60 231... 

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... 

C-14 and C-29 to C-33. The structures of the bastadins have in most cases been elucidated through the application of standard spectroscopic techniques, although those of bastadin 4 and the tetramethyl ether of bastadin 5 have been established through X-ray crystallography [119]. 

Bioassay guided fractionation of the methanol extract of an Indonesian sample of I. hasta resulted in the isolation of a total of eight bastadins representing each of the three structural motifs found in the series [128,129]. Bastadin 6 (114) was isolated as the major bioactive constituent of the sponge and inhibited the VEGF- and... 

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

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