Reviews of indole-ring synthesis

In addition to the general reviews of indole ring synthesis cited in Chapter 1, the Fischer indole synthesis per se has been extensively reviewed [6-10]. The excellent documentation (>3000 citations in reference 8) will not be repeated here. Rather in this chapter, I focus on recent applications in drug development, materials discovery, and natural-product synthesis. 

For a review of recent methods for indole ring synthesis, see Gribble, G.W. J. Chem. Soc., Perkin Trans. I, 2000, 1045. 

Synthetically attractive indolisation procedures and new methods for the preparation of selectively substituted indoles , Pindur, U. and Adam, R., J. Heterocycl. Chem., 1988, 25, 1 Recent developments in indole ring synthesis - methodology and applications , Gribble, G. W., J. Chem. Soc., Perkin Trans. 1, 2000, and previous reviews in the series. 

From its early isolation by Baeyer from the reaction of indigo with a mixture of sulfuric acid and sulfuric anhydride [1], indole—indigo+o/eum— has a remarkable history and has made a huge impact on society, as we will see in this chapter. The reader is referred to several general reviews on the chemistry and synthesis of indoles [2-11] and their role in society [12], Reviews devoted solely to indole ring synthesis are tabulated in Section 7 in this chapter. 

S.A. PatU, R. PatU, and D.D. Miller, Microwave-Assisted Synthesis of MedicinaUy Relevant Indoles, Cum Med. Chem., 2011,18, 615-637. An excellent review highlighting the utility of microwave heating in indole ring synthesis. 

Fuknyama and colleagnes employed this indole ring synthesis in total syntheses of ( )-vincadifformine [11], (-)-tabersonine [11], (-)-vindoline [13], (-)-aspidophytine [15, 16], and tryprostatins A and B [17]. For reviews of isocyanide-based indole synthesis and organic synthesis using isocyanides in general, see Campo and colleagnes and Tobisu and colleagues [19,20],... 

Given the truly voluminous literature on palladium-catalyzed indole ring synthesis and the large number of recent reviews on this topic [1-11], coverage in this chapter and in succeeding ones is strictly limited. Additional reviews are cited in Chapter 1. 

The Leimgruber-Batcho synthesis is a two-step method which provides indoles that arc substituted only in the benzene ring. The method was initially disclosed in a patent[l] and a representative procedure is available in Organic Syntheses[2]. A review of the reaction is available[3]. The reaction involves... 

Aromatic azapentalenes have not been found naturally, though an imidazo[4,5-d]imidazole derivative has been implicated in the prebiotic synthesis of purines130 74 (see also Section III,A,l,d). Saturated derivatives occur fairly widely the Senecio alkaloids contain the reduced pyrrolol l,2-a]pyrrole (pyrrolizidine) skeleton,487 and the alkaloid withasomnine is a derivative of pyrrolo[ l,2-6]pyrazole.374,488 The mitomycin antibiotics mentioned earlier in this review (Sections III,B,l,f and III,B,5) contain the pyrrolol l,2-a]indole ring,166,331 and the recently reported fungal metabolite sporidesmin is a saturated derivative of pyrrolo[2,3-6]indole.489... 

The progress in synthesis and chemistry of pyrroles, indoles, and related fused ring systems are the subjects of this chapter. Due to space limitations, only a selection of the recent advances reported during the period of January-December 2003 has been included in this text. However, several specialized reviews on the chemistry of indoles and pyrroles have appeared during the reporting period of this account, providing more in-depth coverage. 

The synthesis of indoles on soHd supports has been driven by the wide range of indole derivatives that occur in Nature [142-144], and by the biological activity of many indole derivatives of both natural and synthetic origin [145]. The indole scaffold appears in the amino acid tryptophan, the metabolites of which are important in the biochemistry of both plants and animals. In addition, the indole ring appears in many compounds that have found use as drugs, e.g., indomethacin [146], sumatriptan [147], and pindolol [148]. Synthetic approaches towards indoles on solid phases have also been reviewed elsewhere [149]. 

---