Polycitones

The isolation from a marine ascidian and subsequent structure determination of polycitone A (105) (Fig. 6) was first reported [52] by Kashman and coworkers in 1994. In this paper, the penta-O-methyl derivative was reported to inhibit the growth of SV40 transformed fibroblast cells at a concentration of 10 jtg/mL. Loya, Hizi and Kashman published [53] an extensive account of the biological activity of polycitone A in 1999 in which case inhibition of retroviral reverse transcriptases and cellular DNA polymerases was described. The isolation from an ascidian and structure determination of polycitone B (106) (Fig. 4) was subsequently reported [54] by Kashman and coworkers in 2000. Obviously, the presence of extensive bromination in both polycitone A and B make this family of compounds unique among the 3,4-diarylpyrrole natural products. 

Scheme 21 Steglich Group Synthesis of Polycitone Natural Products...

Decatromicins A (1218) and B (1219) are produced by an Actinomadura sp. and are active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (1229,1230). These compounds are closely related to pyrrolosporin A (1220) from Micromonospora sp. (1231,1232). The ascidian Polycitor africanus from Madagascar has afforded the new polycitone B (1221) (1233), which is related to the known polycitone A (1), a potent inhibitor of retroviral reverse transcriptases and cellular DNA polymerases (1234). The known polycitrin B was synthesized for the first time (1235). 

Rudi A, Evan T, Aknin M, Kashman Y (2000) Polycitone B and Prepolycitrin A Two Novel Alkaloids from the Marine Ascidian Polycitor africanus. J Nat Prod 63 832... 

Loya S, Rudi A, Kashman Y, Hizi A (1999) Polycitone A, a Novel and Potent General Inhibitor of Retroviral Reverse Transcriptases and Cellular DNA Polymerases. Biochem J 344 85... 

A type Had cyclization of vinamidinium salt 24 with a-aminoacetophenone 25 in the presence of sodium hydride led to the formation of 2-keto-4-arylpyrrole 26 <05T1845>. The latter was utilized in a regiocontroUed preparation of the polycitone alkaloids. Vinamidinium salt 24 was readily available from phenylacetic acid 23 by a Vilsmeier-Haack type process. 

As part of their ongoing investigation of bioactive natural products from tropical marine invertebrates collected in Sodwana Bay (situated in northern Kwazulu-Natal, South Africa), Kashman and co-workers isolated three novel alkaloids, polycitone A (89) and polycitrins A and B (90 and 91) from an ascidian Polycitor sp. [86]. The structure of 89 was established from X-ray data while the structures of 90 and its mono-O-methyl ether analogue, 91, followed from analysis of the NMR data of these two compounds. Two possible biosynthetic precursors of 89-91,... 

Among the most highly substituted of the pyrrole derivatives reported from ascidians to date, is polycitone-A (84), which was isolated along with polycitrins A and B from a tunicate of the genus Polycitor [44]. The biosynthetic processes which lead to (substituted) phenacyl substituents... 

Rudi, A., Evan, T., Aknin, M., Kaslunan, Y., (2000). Polycitone B and Prepolycitrin A Two novel alkaloids from the marine ascidian Polycitor africanus. J. Nat. Prod. 63, 832-833. 

Loya, S., Rudi, A., Kashman, Y., and Hizi, A. (1999) Polycitone A, a novel and potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerase. Biochem. J., 344, 85-92. 

Gupton, J.T., Banner, E.J., Sartin, M.D., Coppock, M.B., Hempel, J.E., idtarlamova. A., Fisher, D.C., Giglio, B.C., Smith, K.L., Keough, M.J., Smith, T.M., Kanters, R.P.F., Dominey, R.N., and Sikorski, J.A. (2008) The application of vinylogous iminimn salt derivatives and microwave accelerated Vilsmeier-Haack reactions to efficient relay syntheses of the polycitone and stomiamide natural products. Tetrahedron, 64, 5246-5253. 

There are a number bromotyrosine derived compounds not belonging to any of the above structure classes. Geodiamolides, a series of cyclic depsipeptides, are included in this review since they contain halogenated tyrosine. Polycitones and polydtrins are condensation products of substituted bromotyrosine molecules, isolated from ascidians, and are also included in this review. Similar structures including lamellarins are not included due to the absence of halogenation. For the same reason, polyandrocarpamides A-C (253-255), chelonin B (256), and 5-bromochelonin B (257) are included. 

Polycitone A (280) and B (281), polycitrin A (282) and B (283), and prepolycitrin A (284) were reported from the Indo-Pacific ascidians Polycitor sp. and P. africanus by Kashman s group (167,168). Their structures were established by spectroscopic and chemical methods. The structure of polycitone A (280) was confirmed by X-ray crystallography (167). 

The structures of polycitone A (280) and B (281) and polycitrin A (282) and B (283) were close to the lamellarins isolated from the mollusk Lamellaria sp. (169) and an ascidian of the genus Didemnum (170,171). Lammellarins are not included in this review because of the absence of a halogen in their structures. A possible biogenetic... 

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