Bastadins structure

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... 

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... 

Crews has formulated a collective scheme for the biosynthesis of the sponge metabolite bastadins based on the knovm structures (Scheme 19.8) [123]. Thus, dimerization of two brominated tyrosines can lead to hemibastadins 14S, which in turn can couple to form prebastadins 146. Final ring closure can afford bastadins 147 or isobastadins 148. The final cyclization is similar to the formation of polybromi-nated dibenzo-p-dioxins from polybrominated diphenyl ethers, which are ubiquitous in sponges [124,125]. 

The remaining 20 bastadins possess a macrocyclic system, which was given a name bastarane and numbered as shown (129). According to the oxidative cycli-zation, there are two structural classes, i.e. 13,23-dioxa-4,22-diazabastarane and 13,32-dioxa-4,22-diazaisobastarane (131). 

The studies of bastadins 8-13 were published simultaneously, unfortunately leading to the assignment of the same number to different bastadins. Scheuer et al. suggested that these alkaloids be renamed in the order of when they were received for publication. Thus, bastadins-8 to -11 of Pordesimo and Schmitz (132) retained their original numbering, bastadin-9 of Miao et al. (142) was renumbered as bastadin-12 (bastadin-8 from Miao et al. coincidentally has the same structure as bastadin-8 of Pordesimo and Schmitz), and bastadin-12 of Butler et al. (131) became bastadin-13. 

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. 

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