Bisindolylation

Of special importance to the synthesis was the choice of condensing agents and cbnditions. HATU-HOAF was of particular value in these final stages. Condensation of the threonine carboxyl of 24 (from Scheme 5) with the pyrrolidine N s of the bisindolyl compound 15 (from Scheme 3) afforded 25. Removal... 

The possibility of replacing all three phenyl rings in the triarylmethane lactone structure by heterocycles has also been exploited. The first compound to be described83 was the 3,3-bisindolyl-7-azaphthalide (18). This... 

Somei et al. reported the total synthesis of the cytotoxic and antiviral 5-cyano-6-methoxy-ll-methylindolo[2,3-fl]carbazole (357) starting from indigo (1458) (786,787). A reduction of indigo (1458) with tin in acetic acid/acetic anhydride afforded 3-acetoxy-2,2 -bisindolyl (1459) in 88% yield. Heating of 1459 with dichloroacetyl chloride in ethyl acetate under reflux provided 3-acetoxy-3 -dichloroacetyl-2,2 -bisindolyl (1460), which was treated with aqueous ammonia in methanol/DMF at room temperature to give the indolo[2,3-fl] carbazole derivative 1461. N-Methylation... 

The indole[2,3-a]carbazole 185 possessing the rebeccamycin aglycone unit [122-132,135,136] was synthesized from the reaction of N-methyl-maleimide and 2,2/-bisindolyl 181 via Michael type addition. In the presence of aluminum trichloride, the bisindole reacts to form the Michael adducts 182 and 183. The mono-Michael adduct 182 was dehydrogenated in the presence of Pd/C in a one pot procedure to produce 184 and 185 (Scheme 43) [ 137]. 

Asterriquinone, the pigment isolated earlier from Aspergillus terreus, proves to be one of eleven closely related pigments, based on a bisindolyl-p-benzoquinone skeleton substituted at positions 1, 2 or 7 of the indole rings by isoprene or... 

The initial product 508 of AFC reactions of aromatic aldehydes, primary amines, and indoles is highly reactive and further addition of indoles gives undesired adduct 509 (Scheme 104) <2006OL4939>. In addition, aromatic aldehydes are themselves known to react with indoles directly to afford the undesired bisindolyl product 509. After screening catalysts (AcOH, TFA, Sc(DS)3, dodecylbenzenesulfonic acid, carboxylic acids from -C7Hi5 to -Ci3H27), it was revealed that decanoic acid ( -C9Hi9C02H) efficiently promoted the reaction without formation of product 509. 

Synthesis of himastatin involved the preparation of the pyrroloindoline moiety A, its conversion to the bisindolyl unit A 2, synthesis of the peptidal ester moiety B, the subsequent joining of these units (A 2 and two B units), and cyclization leading to himastatin. The following brief account focuses on the protective group aspects of the synthesis. 

The TBS group then had to be replaced (two steps, Scheme 3 a and b) by the more easily removable TES (triethylsilyl) group to permit deblocking at the last step in the synthesis of himastatin. Before combination of the bisindolyl unit with the peptidal ester unit, several additional changes in the state of protection at the two nitrogens... 

There are several indications, mainly in the patent literature, of possible uses of tetrahydroquinoxalines. Derivatives related in structure to Hetrazan (l-diethylcarbamoyl-4-methylpiperazine) have been prepared as potential drugs for the treatment of filarial infections. Other tetrahydroquinoxalines of type 43 have been screened for antineoplastic activity and bisindolyl derivatives of type 44 have been claimed to have a wide spectrum of biological activity. Tetrahydroquinoxaline phosphates and thiophosphates have been patented as insecticides, and other tetrahydroquinoxalines have been patented for protecting rubber against... 

Merlic took advantage of the Cadogan reaction to make bisindoles. Thus cyclization of fra 5 -stilbene 38 with triethyl phosphite resulted in unsymmetrical 2,2 -bisindolyl 39 in modest yield. 

The proposed Si-face stereoinduction model involves stabilization of the Lewis acid-carbonyl complex with a formyl iZ-bond to the BINOL ether oxygen (l l complex of ethyl glyoxal 90). Replacement of the formyl hydrogen with an alkyl group provided little of the expected product with the bisindolyl alkylated side adduct (91) predominating and minimal stereocontrol for the associated adduct (not shown in scheme, 10% ee). 

Bandini and Umani-Ronchi et al. again used InBr3 in the syntheses of 1,3-bisindolyl compounds after confirming its superiority over AICI3 and InCl3. In addition, they found that the addition of TMSCl increased yield and halved the reaction time [55] (Figure 8.29). 

Fig. 8.29 Syntheses of 1,3-bisindolyl compounds through a Michael addition strategy.

Platinum(II) chloride-catalysed reaction of allenes R R C=C=CHR with N-protected indoles (In) in THF with added MeOH proceeds at 70 C over 20 h and affords products of geminal bisindolylation, that is, R R CH-CH2C(3-In)2R. By contrast, gold(I) complexes catalyse monoindolylation, giving rise to allyl indoles... 

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