Eudistomins from Eudistoma olivaceum

An additional sulfur-containing P-carboline belonging to the eudistomin family, N( 10)-methyleudistomin E (478) was obtained from the Caribbean tunicate Eudistoma olivaceum [363]. 

Radiotracer experiments were used to elucidate the biosynthetic precursors to eudistomin H (7) and I (8) in Floridian collections of Eudistoma olivaceum. Both radiolabeled tryptophan and proline were incorporated by E. olivaceum into eudistomins H and I and tryptamine was incorporated into eudistomin I, to the exclusion of eudistomin H. Bromotryptamine and bromotryptophan are incorporated into eudistomin H (Scheme 30). These results suggest eudistomin biosynthesis proceeds from the amino acids via decarboxylation, halogenation, then condensation with proline. 

The manzamine alkaloids are characterized by a complex pentacyclic diamine linked to C-l of a B-carboline moiety. The first B-carboline compound (norharman and harman) was reported from a bioluminiscent marine dino-flagellate Noctiluca miliaris [31], followed by the discovery of the eudistomins from Eudistoma olivaceum [32, 33, 34], Their occurrence has been reported not only from sponges and tunicates, but also from the Bryozoan Costaticella hastata [35], and Cribricellina cribraria [36] and lately from the Cnidaria (Villagorgia rubra) exemplified by the Villagorgins [37]. 

Rinehart, K.L. Kobayashi, J. Harbour, G.C. Hughes, R.G. Mizsak, S.A. Scahill, T.A. Eudistomins C E K and L Potent Antiviral Compounds Containing Novel Oxathiazepine Ring from Caribbean Tunicate Eudistoma olivaceum. J. Am. Chem. Soc. 1984, 106, 1524-1526. 

The )8-carboline system alkylated at C-1 occurs frequently in the indole alkaloid series and in some cases in the 1,2,3,4-tetrahydro form, as shown above. The simplest homolog with a methyl substituent is caUed harman (Fig. 12). It has been found in several plant families and also in the higher fungus Coriolus maximus (174). Recently, particular interest in 1-substituted /3-carboline derivatives has also resulted from the antiviral activity against herpes simplex virus type 1 (HSV-1) discovered in eudis-tomins alkaloids (e.g., eudistomin S Fig. 12), isolated from the tunicate organism Eudistoma olivaceum (175). 

The eudistomins are a class of polycyclic alkaloids that contain a unique 1,3,7-oxathiazepine ring system as well as an iV,iV,0-trisubstituted hydrojq lamine substructure (Scheme 15.7). These natural products were isolated by Rinehart et al from the colonial tunicate Eudistoma olivaceum in 1984, and they exhibited strong antiviral activity against the Herpes sinplex... 

Rinehart KL, Kobayashi J, Harbour GC, Hughes RG Jr, Mizask SA, Scahill TA (1984) Eudistomins C, E, K, and L, potent antiviral compounds containing a novel oxathiazepine ring from the Caribbean tunicate Eudistoma olivaceum. J Am Chem Soc 106 1524-1526... 

Rinehart KL, Kobayashi J, Harbour GC, Gilmore J, Mascal M, Holt TG, Shield LS, Lafargue R Eudistomins A-Q, 8-Carbolines from the antiviral Caribbean tunicate Eudistoma olivaceum. J. Am. Chem. Soc. 1987 109(ll) 3378-3387. 

Still, I.W.J. and McNulty, J. (1989) The synthesis of eudistomins S and T 3-carbolines from the tunicate Eudistoma olivaceum. Heterocydes, 29, 2057-2059. 

Eudistomin K (155) (135) and its sulfoxide (171) (136) were isolated from the New Zealand ascidian Ritterella sigillinoides. The sulfoxide (171) also shows antiviral activity. The structure of 155 was determined by X-ray analysis (137) and that of 171 by semisynthesis from 155. Three other /3-carbolines, named eudistomins R, S, and T (172-174) were obtained from a Bermudian tunicate (E. olivaceum) by using an amino-bonded HPLC column (138). A 2-methyl-1,2,3,4-tetrahydro- -carboline with an /V-methylpyrrolidine at C-l, named woodinine (175), was isolated from a New Caledonian ascidian (Eudistoma fragum) (139), extracts of which exhibit antimicrobial activity. 

The eudistomins constitute a broad family of P-carboline alkaloids which are found mainly in the genus Eudistoma (mostly from E. olivaceum) but also in a few species of Lissoclinum (eudistomine U, isolated from L. vareau see above) and in Ritterella (see below), which all belong to the order Aplousobranchia. This series of alkaloids was discovered in 1978 during the same expedition of the American vessel Alpha Helix that led to the discovery of the didemnins. The 30 eudistomins currently known are almost all brominated and may be divided into four structural types, which are presented in Figure 28.19. 

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