Dragmacidin alkaloids

A unified synthetic approach to the pyrazinone-containing dragmacidin alkaloids 06CC3769. 

Kohmoto, S. Kashman, Y. McConnell, O.J. Rinehart, K.L., Jr. Wright, A. Koehn, F. (1988) Dragmacidin, a new cytotoxic bis(indole) alkaloid from a deep water marine sponge, Dragmacidon sp. J. Org. Chem., 55,3116-8. 

Cutignano, A., Bifulco, G., Bruno, I., Casapullo, A., Gomez-Paloma, L., and Riccio, R. (2000). Dragmacidin F A new antiviral bromoindole alkaloid from the Mediterranean sponge Halicortex spp. Tetrahedron 56, 3743-3748. 

The tribrominated bisindole alkaloid dragmacidin (30) from the marine sponge Dragmacidon sp. has antitumor activity against P-388 cells (IC5o 15 pg/ml), A-549 (human lung), HCT-8 (human colon), and MDAMB (human mammary) cancer cell lines (IC501-10 pg/ml) [43]. 

Cutignano A, Bifulco G, Bruno I, Casapullo A, Gomez-Paloma L, Riccio R (2000) Dragmacidin F A New Antiviral Bromoindole Alkaloid from the Mediterranean Sponge Halicortex sp. Tetrahedron 56 3743... 

A new set of Mannich bases of 10//-indolo[3,2-6]quinoxaline was prepared <02IJH157>. A versatile synthetic route to /V-protected L-amino acid (3-benzylquinoxalin-2-yl)hydrazides was developed <02LPS49>. The properly substituted bis(indole) pyrazine 165 from the marine alkaloid dragmacidin D was prepared from 2,5-dibromo-3-methoxypyrazine (164) <02JOC9392>. 

As part of the synthetic methodology for the synthesis of the cytotoxic marine alkaloid, dragmacidin, 6,7-dibromo-4-methoxyisatin was reduced to the corresponding indole in 33% yield using a commercial solution of 1M BH3.THF128. 

Marine alkaloids were also reported to possess activity in vitro against AIDS-opportunistic infectious diseases such as tuberculosis and toxoplasmosis [53,54]. Examples of these alkaloids included the ascidian alkaloids lamellarins. Fig. (5) [55], and dragmacidin F, Fig. (6), a new... 

Marine sponges have been shown to be a prolific source of anti-HSV alkaloids. Dragmacidin F, Fig. (6) is a new antiviral bromoindole alkaloid isolated from the Mediterranean sponge Halicortex spp. collected from the south coast of Ustica Island, Italy [56]. This compound. 

Research by B. Jiang et al. showed that the asymmetric aminohydroxyiation of vinyl indoles can afford (S)-A/-Boc protected a-indol-3-ylglycinols in moderate to good yield and with up to 94% ee. The use of these enantiopure intermediates allowed the short enantioselective total synthesis of bisindole alkaloids, such as dragmacidin A, which contains a piperazine moiety between the indole rings. 

Yang, C.-G., Wang, J., Tang, X.-X., Jiang, B. Asymmetric aminohydroxylation of vinyl indoles a short enantioselective synthesis of the bisindole alkaloids dihydrohamacanthin A and dragmacidin A. Tetrahedron Asymmetry 2002, 13, 383-394. 

A synthesis of the marine alkaloid (+)-dragmacidin F featured the oxidative cyclization of pyrrole 50 to give 51 in good yield [43], Further elaboration to the natural product involved a Suzuki coupling (Section 2.3.3). 

A direct approach for selective construction of properly substituted bis(indole) pyrazine 100, the skeleton of a marine alkaloid dragmacidin D, has been reported. The Suzuki and the Stille cross-coupling reactions are key steps involved for regioselective introduction of two indole units [6]. 

Indole alkaloid dragmacidin E, 108-109 Indole alkaloid ibogaine anxiolyticlike, 267-269... 

The antiviral bromoindole alkaloid dragmacidin F and the potent natural antitumor agent (-f-)-dynemicin A involve a Suzuki coupling in one of the key carbon-carbon bond-forming steps (Figure 10.1) [8, 9). Further examples of industrially prepared fine chemicals involving palladium-catalyzed cross-coupling... 

Miscellaneous Processes. A versatile synthetic route to the pyrrolophenanthridone alkaloids has been developed that involves a palladium-mediated cyclization of iV-benzoyl indolines, then 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (DDQ)-promoted oxidation of the resulting dihydropyrrolophenanthridones. Related processes have been exploited in an elegant total synthesis of the marine alkaloid (+)-dragmacidin F and in the preparation of biologically relevant indoles. 202.203... 

The Amdt-Eistert homologation is equally applicable to the synthesis of alkaloids. For example, Stoltz demonstrated its application to the first synthesis of the bis-indole alkaloid dragmacidin D (38). In the final steps of the synthesis, carboxylic acid 36 was homologated to the diazo ketone, which was subsequently exposed to hydrobromic acid. This gave a-bromo ketone 37, which was elaborated to racemic dragmacidin D (38). 

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