Indole bases, simple

Banerjee, P.K and S. Ghosal 1969. Simple indole bases of Desmodium gangeticum (Leguminosae) Australian Journal of Chemistry 22 275-277,... 

Table I is a compilation of plant species which contain the simple indole alkaloid types of Fig. 1. As mentioned earlier, the main requirement for the inclusion of a certain simple indole alkaloid into Table I is that it contain a tryptamine unit as a readily distinguishable feature in its structure. That tryptamine is a precursor in the biosynthesis of many of the b, c, d, and e type simple indole bases is yet to be shown although it is felt that future work will prove the correctness of such a view. Gramine, the simplest indole alkaloid, has been included in the tryptamine classification a because it is biosynthetically related to tryptophan cryptole-pine has been likewise included therein although its structural relationship to tryptophan appears more obscure (Volume VIII, Chapter 1, pp. 4, 19). The calycanthine type does not possess a tryptamine structure but it is included in the simple indole alkaloid b classification since most of its congeners are tryptamine derivatives and since it exhibits a close biogenetic relationship to this latter (chimonanthine) type (Volume VIII, Chapter 16). Type d is represented by the small number of the so-called canthin-6-one alkaloids (Volume VIII, pp. 260-252, 497-498). The most recent variation of the simple indole alkaloids is found in the Anacardiaceae family. Its indoloquinolizidine nucleus suggests inclusion with type d on the basis of structural and biogenetic similarity. Finally, simple indole alkaloid type e is composed of the well-defined evodiamine (rutaecarpine) structural form (Volume VIII, Chapter 4).

Wender and White published a very simple indole ring synthesis that involves the generation of a bis-lithio anion 1 and its reaction with an a-halo carbonyl compound 2, followed by acid- or base-catalyzed dehydration [1,2], The overall transformation is shown in Scheme 1, along with three examples. This chemistry illustrates yet another indole ring synthesis that uses a-halo carbonyl compounds [3]. We will encounter these compounds again with the venerable Bischler indole synthesis in Chapter 23. A summary of several Wender indole ring syntheses is tabulated in Table 1 [1, 2, 4-7], Entry 5 features a directed lithiation method to the bis-lithio nucleophile [5], a modification also described by Wender and White [2], Sainsbury and... 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Clemo, Perkin and Robinson have recorded the production of indole and carbazole when methylstrychnine is heated with caustic potash, and more recently a series of simple bases has been obtained by the alkaline degradation of strychnine. Of these, tryptamine (j8-3-indolylethylamine), 3-ethylindole, indole and 4-methyl-3-ethylpyridine have been identified, and a fifth purified as the picrate, CjoHuN. CgH30,N3, m.p. 192°, has been described by Clemo and by Siddiqui, but has not been identified. Tryptamine is to be expected as the Robinson formula includes the tryptamine skeleton. ... 

This structure rationalizes (a) the formation of mono- and, under more vigorous conditions, tetra-acetyl derivatives, (b) the methyla-tion to a dimethyl derivative still containing two active hydrogens, (c) the pyrolysis back to monomeric indole, (d) the formation of a benzylidene derivative containing the Ph CH=N— Ar ehromophore, (e) the failure to form a simple nitroso derivative, (f) the Zn/AcOH reduction of the dimethyl trimer to base C18H20N2, shown to be identical with the dihydro derivative of (26). 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

It is interesting to note that this methodology allows the preparation of 4-functionalized indole derivatives starting from a simple acyclic precursor in a one-pot sequence. To prepare N-unsubstituted indoles, we choose the allyl moiety as a result to its stability to strong basic conditions and the variety of methods for its removal.[20] We therefore used an approach based on the isomerization/hydrolysis of the allyl groups with diisobutylaluminium hydride (DIBAL-H) and a... 

Two recently published procedures should be highlighted. Development of simple and scalable one-step biotransformation of 4.5.6.7-halogenated (F, Cl, Br) and methylated indoles into the appropriate tryptophan analogues (Fig. 3) is based on 3-days incubation of a bacterial lysate together with L-serine at 37°C [63]. 

---