Aplysamine

Similarly, Aplysina sp.(Fig. 10.7), which show a dramatic change in color from yellow to black when exposed to air, contain cytotoxic compounds including bromotyrosine-derivative alkaloids, purealidins (Ishibashi et ah, 1991 Yagi et ah, 1993), aplysamine 2 (Xynas and Capon, 1989), and purpuramin G (Fattorusso et ah, 1970 Fig. 10.8). 

Kijjoa A, Bessa J, WattanadilokR, SawangwongP, Nascimento MSJ, Pedro M, Silva AMS, Eaton G, van Soest R, Herz W (2005) Dibromotyrosine Derivatives, a Maleimide, Aplysamine-2 and Other Constituents of the Marine Sponge Pseudoceratina purpurea. Z Naturforsch 60b 904... 

Buchanan et al. have also identified another bromotyrosine scaffold containing natural product that possesses Icmt inhibition, named aplysa-mine 6 (C, Figure 9.8) [73]. Aplysamine 6 is also an alkaloid derived from Pseudoceratina sp. however, it does not have an oxime and is not symmetrical as opposed to spermatinamine. An IC50 of 14 pM is reported for aplysamine 6, significantly higher than the other extract. 

Fio. 9.8. Structures of nonsubstrate-based Icmt inhibitors (A) cysmethynil, (B) spermatinamine, (C) aplysamine 6. 

Buchanan, M.S., et al (2008). Aplysamine 6, an alkaloidal inhibitor of Isoprenylcysteine carboxyl methyltransferase from the sponge Pseudoceratina sp. J Nat Prod 71 7. 

Organ and coworkers developed a microwave-assisted flow system, which was used successfully for the synthesis of a key intermediate of the ICMT (isoprenylcysteine carboxylmethyltransferase) inhibitor aplysamine 6 (Scheme 1.33) [89]. 

Scheme 1.33 The microwave-assisted flow chemistry procedure to a key aplysamine intermediate developed by Organ s group [89].

Yoshida, M. and Yamaguchi, K (2008) Total synthesis of dispyrin, purpurealidin E, and aplysamine-1. Chem. Pharm. BuU., 56,1362-1363. 

Different iV-methylation derivatives of moloka iamine, aplysamine 1 (54) 44), purealidin F (55), and G (56) 45), were obtained from an Australian sponge Aplysina sp. and the Okinawan sponge Pscanmaplysilla purea, respectively. 3,5-Dibromo-4-(3-dimethylaminopropoxy)phenethyl carbamic acid methyl ester (57) and its salt 58 were obtained as the first bromotyrosine derivatives containing a carbamate group from an Indian sample of Psammaplysilla purpurea 46), along with 59 47,48). 

Xynas and Capon reported aplysamine 2 (172) from an Australian marine sponge Aplysina sp. in 1989 (44). Aplysamines 3 (173), 4 (174), and 5 (175) were isolated from the Hawaiian sponge Psammaplysilla purpurea by Scheuer s group (118). All of these alkaloids exhibited cytotoxic activity, while aplysamine 3 and 4 showed mild antibacterial activity against Staphylococcus aureus. Alkaloids 176 and 177 were isolated from the sponge P. purpurea collected in Okinawa by an Indian group (119,120). 

Purpuramines A-I (179-187) exhibited antibacterial activity against Staphylococcus aureus, but phenylpymvic acid oxime (188) was not active. Purpuramine J (189) was isolated from the Fijian sponge Psammaplysilla (Druinella) sp., along with purpuramine I (187), aplysamine 2 (172), and eight other bromotyrosine derivatives (86). Purpuramine J (189) is the first bromotyrosine derivative containing an A-oxide functionality, which is considered rare in marine natural products. 

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