Pyrrolo indoles, synthesis

As lactams of 4-amino-3-oxobutanoic acids, tetramic acids react with amines (87JPJ858) and with phenylhydrazine. The latter reaction is catalyzed with para-toluenesulfonic acid. Thus, for example, l/2b give phenyl-hydrazone 65 in 80% yield that, in turn, under the conditions of the Fischer indole synthesis, may give rise to pyrrolo[4,3-b]indolene 66 (90TH1). (See Fig. 31.)... 

Pyrrolo[l, 2-a]imidazoI-2(3 ff)-ones synthesis, 6, 1001 Pyrrolo[3,2-6]indoles synthesis, 4, 243 Pyrrolo[3,2-/]indolizines synthesis, 4, 274, 296 Pyrroloisoquinolines synthesis, 4, 513... 

The treatment of /Vb-methoxycarbonyl-L-tryptophan methyl ester (9) with trifluoroacetic anhydride in trifluoroacetic acid gave directly the A -trifl uoroacetyl cyclic tautomer with excellent diastereoselectivity [90% yield, endo/exo 97 3 ( ll NMR)]60. Furthermore, pure A a-sulfonyl-entfo-derivatives (X-ray) were prepared from lo206,61 and were employed to prepare homochiral a-, / -, and a, -substituted tryptophan derivatives and pyrrolo[2,3-b]indole alkaloids206 59 62. Similarly, the /Va-acetyl-enc/o-pyrrolo-indole 10 was used for the synthesis of 5-substituted L-tryptophan derivatives63,64. 

An interesting new approach to pyrrolo[l,2-a]indole synthesis was developed by Kozikowski and Mugrage [53]. Their route began with 2-amino-acetophenone 163 (Scheme 23), which was tosylated and then treated with... 

The Fischer indole synthesis and its variations are prominently highlighted in the synthesis or partial synthesis of many natural products, many of which are summarized in Table 7 [288-311]. In addition to these examples, Fischer indolization was often applied to the synthesis of pyrrolo[2,3-( ]indole alkaloids in what Southwick in 1963 coined an arrested Fischer indole synthesis [312], later to be expanded by Garg as an interrupted Fischer indolization [313-317], as featured in his elegant syntheses of... 

Diaryl-substituted pyrrolo[3,2-6]pyridine-5-carbonitriles 63 exhibiting c-Met receptor tyrosine kinase inhibition activity were reported. The key intermediates 64 were prepared using the Larock indole synthesis. A variety of aryl/heteroaryl substitution in the 2-position was then efficiently explored from the corresponding iodo analogs 65. 

Pvrrolor3.2- 1pvridines The synthesis of the aromatic pyrrolo[3,2- ]pyridine ring system was achieved by a variation of the Leimgruber-Bathcho indole synthesis (9.101 The 5-nitro-6-methylpyridine required by this scheme was prepared by treatment of a solution of nitroacetone and 9 in ethanol at -IQPC with sodium acetate, followed by the addition of ammonium acetate and heating at reflux. This reaction proved to be reproducible, reliably affording 26 in modest yield (44%). 

Interest in the synthesis of the mitomycins has resulted in a variety of procedures for the preparation of pyrrolo-indoles and related structures. Now Ban and his colleagues have reported a biomimetic route to the mitosane skeleton which involves a novel retro-aldol type of ring-opening reaction followed by a trans-annular cyclization (Scheme 102). A mitosane-like compound is available via... 

Indolo[3,2-fl]pyrrolo[3,4-c]carbazoles 120 have been obtained in one step from indole and the corresponding maleimides in acetic acid, with coformation of the Michael adducts 121 (Scheme 15). This reactitai required careful temperature control in order to obtain the desired product ratios. An alternative independent synthesis of compounds 120 could also be accompKshed from 2,3 -biindolyl (115) andsuitable maleimides in hot acetic acid (99T2363). The system 120 where R = H has also been reported as a minor product during studies toward a synthesis of the alkaloid arcyriaflavin A (95TL2689). 

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