Indoles dragmacidin

Following these early investigations on the Bartoli indole synthesis, several research groups made use of this reaction to great effect as a starting point in natural product synthesis despite the inherent low to modest yields. Stolz employed the Bartoli synthesis to prepare 7-benzyloxy-4-bromoindole (33% yield from 2-benzyloxy-5-bromoni-(robenzene and vinylmagnesium bromide) in the first total synthesis of the marine bis-indole ( )-dragmacidin D [24]. 

A route to an intermediate 87 containing the core system of dragmacidin has been described, which involved the three-point fusion of an indole onto the seven-membered ring... 

Dragmacidon sp., Axinel., Pwit dragmacidin (bis-indole alkal.), C 8.2.A/cytotoxic on human tumcH cells Kohmoto 1988 (also from Spongosorites sp., Halichon., Porif from deep-waters in S. Australia Capon 1998)... 

Spongosorites sp. Halichon., Porif. dragmacidin E (bis-indole alkal.)/inhibitor of serine-threcnine protein phosphatases Capon 1998... 

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. 

Dragmacidin E synthesis studies. Preparation of a model cycloheptannelated indole fragment. Organic Letters, 7, 5449-5452. 

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. 

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. 

The constrnction of the dragmacidin E core ring system 107 proceeds via two Stille cross-couplings with A-tosyl-3-(tri-n-butylstannyl)-indole and 105 (Scheme 5.4.20).This synthesis also features an application of a new indole annnlation reaction.99... 

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... 

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