Eudistomidin

Malbrancheamide (60) represents a novel type of CaM inhibitors although other natural indole alkaloids such as the unusual indole-carbazole alkaloids from a culture broth of a Nocardiopsis sp, namely K-252a-K252d, the brominated P-carbolines eudistomidins A and C, obtained... 

KobayashiJ, NakamuraH, Ohizumi Y, HirataY, Eudistomidin-A, anovelcalmodulin antagonist from the Okinawan tunicate Eudistoma glaucus, Tetrahedron Lett 27 1191-1194, 1986. 

Kobayashi J, Cheng JF, Ohta T Nozoe S, Ohizumi Y, Sasaki T, Eudistomidins B, C, and D Novel antileukemic alkaloids from the Okinawan marine tunicate Eudistoma glaucus, J Org Chem 55 3666—3670, 1990. 

Eudistomidin C (90) was one of three antileukaemic (3-carboline alkaloids isolated from an Okinawan sample of Eudistoma glaucus. It was identified by spectral methods and synthesis of a derivative [114]. Eudistomidins E (91) and F (92) were isolated from E. glaucus from Okinawa and identified by spectroscopic techniques [115]. 

Eudistomidins C (90) and F (92) contain a methyl sulfide group while eudistomidin E (91) contains a methyl sulfoxide. 14-... 

Marine tunicates are a rich source of intriguing structures and interesting biological activities. Eudistomidin A (1) from the Okinawan tunicate Eudistoma glaucus possesses powerful calmodulin antagonistic activity (IC5o 3 x 10 M). Eudistomidins B-D (2-4) show potent cytotoxicity... 

The sulfur-containing P-carboline marine alkaloids isolated from tunicates belong to three main chemical families the eudistomins, the eudistomidins, and the didemnolines. 

The P-carboline alkaloid eudistomidins were isolated from the Okinawan tunicate Eudistoma glaucus. A methyl sulfide group is present in eudistomidins C (27) [30] and E (28) [32] while a methyl sulfoxide occurs in eudistomidin F (29) [32]. Their structures were elucidated on the basis of spectroscopic data. The 5 configuration at C-10 of eudistomidin C (27) was established by synthesis of 10-(/ )-Omethyleudistomidin C [30]. The... 

Eudistomidin A (167) was isolated from an Okinawan tunicate (Eudis-toma glaucus) and exhibited strong calmodulin-antagonistic activity (133). Compound 167 was the first calmodulin antagonist of marine origin and is about 15 times more potent than W-7, a well-known calmodulin antagonist. Eudistomidins B, C, and D (168-170) were obtained from the same... 

The PS reaction has been used by Still and coworkers to prepare woodinine (14), eudistomin T (17), and a eudistomidin B analog (Scheme 8) (125, 126). Woodinine was prepared from l-proline via intermediate 160 the diastereoselectivity of the PS reaction provides roughly an 85/15 ratio of the desired trans isomer. Intermediate 161 has previously been elaborated into eudistomins I (8) (28) and eudistomin H (7) can be derived directly from eudistomin I (127). That woodinine derives from an L-amino acid while the oxathiazepino-eudistomins derive from a D-amino acid is curious from a biosynthetic point of view. 

Eudistomidin A (11) and eudistomins H (7), I (8) and P (9) have been made (127, 128) by the Bischler-Napieralski (BN) reaction, a method used extensively by the Hino group. Appropriately substituted tryptamine was condensed with BOC-prolinoyl chloride, then treated under BN conditions (POCl3 or polyphosphoric ester (PPE)) to produce a 5,7-disubstituted eudistomin skeleton (163). Eudistomin I thus results when starting from tryptamine (Scheme 9, R = R = H), eudistomin H from 5-bromotryptamine (Scheme 9, R = Br, R = H), eudistomidin A from 5-bromo-7-hydroxytryptamine (Scheme 9, R = Br, R = tosylate) eudistomin P is obtained from the use of 6-bromo-5-methoxytryptamine. 

P-Carbolines which have other substituents at Cl include eudistomin U (142) from the Caribbean didemnid Lissoclinum fragile [95], eudistomidins C (143) [96,97], E (144) [98] and F (145) [98] from the Okinawan ascidian Eudistoma glaucus, eudistomins R (146), S (147) and T (148) from the... 

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