Dragmacidins

The Heck cyclization of bromopyrrole 77 and the corresponding oxidative Heck cyclization of desbromopyrrole 78 was studied <06SL3081>. While the Heck cyclization of 77 led to a mixture of [3.3.l]bicycle 79 and [3.2.2]bicycle 80 under a variety of conditions, the oxidative Heck cyclization of 78 led solely to the desired building block 79. The latter has previously been utilized in a total synthesis of dragmacidin F. 

A review discussed the use of 3,5-dichloropyrazin-2-one as a versatile scaffold for synthesis <06S2799>. A feature article was concerned with the synthesis of dragmacidins <06CC3769>. 

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... 

During the total synthesis of Dragmacidin F (537) from quinic acid, Stoltz and col-leagues applied a high-yield late-stage Neber rearrangement to introduce in a completely enantioselective manner an amino group into a complex framework (equation 238). 

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. 

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]. 

Dragmacidins D and E (199) from the Australian sponge Spongosorites sp. inhibit serine-threonine phosphatases [158]. 

Capon RJ, Rooney F, Murray LM, Collins E, Sim ATR, Rostas JAP, Butler MS, Carroll AR (1998) Dragmacidins New Protein Phosphatase Inhibitors from a Southern Australian Deep-Water Marine Sponge, Spongosorites sp. J Nat Prod 61 660... 

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... 

Garg NK, Stoltz BM (2006) A Unified Synthetic Approach to the Pyrazinone Dragmacidins. Chem Commun 3769... 

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>. 

Stepwise double coupling of two different arylboronic acids with a dihaloarene afforded one-pot, two-step method for synthesizing unsymmetrical teraryls, quateraryls, and other higher order polyaryls.882 The first total synthesis of dragmacidin D involved a sequential double coupling of two different pinacol 3-indoleboronic esters (ArBpin Equation (207)).882... 

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. 

Bis-heterocyclie analogues of the current invention such as Dragmacidin F, (IV), Topsentin D, and Topsentin E and their salts have been prepared and are reviewed (5). 

Figure 4 Structures of topsentin class metabolites isolated at HBOI13 (topsentin), 14 (bromotopsentin), 15 (nortopsentin A), 16 (nortopsentin B), 17 (nortopsentin C), 18 (dragmacidin D), 19 (dragmacidin), 20 (2,2-bis(6 -bromoindol-3 -yl)ethylamine), 21 (hamacanthin A), 22 (hamacanthin B)...

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