h2noc^ nh o hn

nostophycin (87)

co2h ch3 o hn nh

microcystin-LR (86)

o c02h o nh x rr^NH2

"oh scytonemin A (88)

"oh scytonemin A (88)

nostophycin (87)

theonegraraide (89)

Yyy° o co2hoh

H2N0CY^nh Jo

theonellamide F (90)

theonellamide F (90)

Scheme 1.5.13. Cyclopeptides related to cyanobacteria (Adda, Ahoa, Ahda, Ahmp and Aboa).

Dolastatins 11, 12 79, 81, first isolated from the sea hare Dolabella auricularia and now clearly considered to be of dietary cyanobacterial origin, can be mentioned as examples [133]. The structurally closely related cyclodepsipeptide majuscula-mide C 80 has been isolated from defined cyanobacterial sources [119]. This was one and a half decades before dolastatin 12 81 was furthermore detected in extracts from a marine cyanobacteria assemblage (Lyngbya majuscula/Schizothrix calcicola)

[134]. Dolastatins 11, 12 79, 81 and majusculamide C 80 contain the aliphatic b-amino acid Map 68.

Ahoa 75 and Ahda 76 are related b-amino-a,d-dihydroxy acids that have been found within cyanobacteria as substructures of the cyclopeptides nostophycin 87 and scytonemin A 88, respectively [11].

The aromatic b-amino acid Adda 74 [114] is a substructure of several cyclopeptides from cyanobacteria, i.e. the microcystins 86 and nodularin 85. More than 60 microcystin and nodularin homologs have already been isolated from the genera Microcystis, Anabaena, and Oscillatoria (microcystins) as well as Nodularia (nodularins). A multitude of literature is available on the biosynthesis and biological activity of these hepatotoxins, which can constitute a serious health hazard in fresh water [135].

Further aliphatic a-methyl-b-amino acids, for example Amha 69, Admpa 70, and Amoa 73, have been found in peptidic natural products from marine animals and from cyanobacteria. Although dolastatin D 82 and dolastatin 17 83 have so far been obtained from sea hare isolates only, these peptides should now be considered to be of cyanobacterial origin, as indicated by their b-amino acid substructures, i.e. Amba 67 and Aoya 72.

Adda 74 has also been encountered in an utterly different source as a substructure of the highly potent protein phosphatase 1 (PP1)-inhibitor motuporin 84. Cyclopeptide 84 was obtained from the marine sponge Theonella swinhoei, a species of the sponge order Lithistida - ''star performers or hosts to the stars'' in natural product synthesis, as Faulkner [136] put it. Further remarkable bicyclic structures of this group are theonegramide 89 and theonellamide F 90, which contain Ahmp 77 or its bromo derivative Aboa 78. Recent microbiological investigations substantiate a correlation between symbiotic filamentous bacteria (not clearly cyanobac-teria) within Theonella sp. and the occurrence of cyclopeptides, especially of those that contain b-amino acids [136].

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