Naturally occurring indoles

Several of the naturally occurring indoles also have clinical importance. The dimeric vinca alkaloid vincristine and closely related compounds were among the first of the anti-mitotic class of chemotherapeutic agents for cancer[14]. The mitomycins[15] and derivatives of ellipticine[16] are other examples of compounds having anti-tumour activity. Reserpine, while not now a major drug, was one of the first compounds to show beneficial effects in treatment of mental disorders[17]... 

Tryptamine and serotonin are naturally occurring indole ethylamino compounds with pronounced pharmaco-... 

Wattenberg LW and Loub WD. 1978. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 38 1410-1413. 

Recognizing that l-(phenylsulfonyl)-3-lithioindole tends to isomerize to the corresponding 2-lithioindole derivative, Bosch et al. used a silyl ether protection to solve the problem. They prepared 3-indolylzinc reagent 36 from 3-bromo-l-(terr-butyldimethylsilyI)indole (35) and then coupled 36 with 2-halopyridine 33 to form 3-(2-pyridyl)indole 37. Finally, the Negishi adduct 37 was further manipulated to a naturally occurring indole alkaloid, ( )-nordasycarpidone (38) [23,27]. 

Some indolizines (90-92) have been prepared because of their structural similarity to naturally occurring indoles tryptophan, gramine, and heterauxin, respectively. 

Applications of Radical Cyclization Reactions in Total Syntheses of Naturally Occurring Indole Alkaloids... 

Finally, although a practical total synthesis of a naturally occurring indole alkaloid using a tandem radical cyclization strategy has yet to be demonstrated this strategy has shown great potential as a powerful tool in indole synthesis. 

Other naturally occurring indoles, auxins, and heteroauxins ... 

Electrooxidation of indole in phosphate buffers gives the trimer 899 (presumably via intermediates 895-898) (Scheme 171) <1998MI47>. The results may provide a deeper insight into the redox chemistry of naturally occurring indoles. At pH > 6.0 the proton abstraction occurs from the intermediate 895 and the reaction proceeds through free radicals and neutral species. 

Streptomyces distallicus the structure elucidation and synthesis have also been made by them.165 A wide variety of porphyrins which are derivatives of porphin (125 R = H) occur in nature and exert three biological functions (a) oxygen storage and transport, as in hemoglobin, (b) cellular respiration as in the cytochromes, and (c) photosynthesis, as in the chlorophylls for detailed discussion of structures and synthesis of naturally occurring porphyrins, see references.166 Recent developments in the chemistry of polypyrrolic compounds have been reviewed.167 Several naturally occurring indole alkaloids have dimeric structures of type B,168 an example of which is c-toxiferine-I, a calabash curare alkaloid found in South American species of Strychnos.169... 

Li, J. J. Applications of palladium chemistry to the total syntheses of naturally occurring indole alkaloids. Alkaloids Chemical and Biological Perspectives 1999, 14, 437-503. 

Since the monumental accomplishments of Woodward s total syntheses of strychnine in 1954 [I] and rcserpinc in 1958 (2], the arsenal of synthetic methods in indole alkaloid synthesis has greatly expanded. In the same time period, the use of palladium chemistry in organic syntheses has also witnessed tremcndou- growth with an ever-expanding repc loire of synthetic methods and their applications to total synthesis. The use of palladium chemistry for the synthesis of indole alkaloids has been explored, and several examples have been included in recent reviews [3-6]. This account attempts to present a comprehensive collection of total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. 

The total synthesis of ellipticine by Miller el al. [11] is one of the first syntheses of naturally occurring indole alkaloids using Pd(OAc), via the oxidative cyclization mechanism (Scheme 2). Exposure of 6-anilino-5,8-dimethylisoquinoline (9) to two equivalents of Pd(OAc)j in TFA/AcOH facilitated the oxidative cyclization to the desired ellipticine (10). Recently, the same indole formation strategy that uses the Pd(OAc),-mediated oxidative cyclization has been the cornerstone of several synthetic approaches directed toward ellipticine analogs. For instance, oxidative cyclization of diphenylamine 11 was carried out with Pd(OAc), in acetic acid to provide... 

Early examples of the total synthesis of naturally occurring indole alkaloids employing the Suzuki reaction include ellipticine (10) as repotted by Miller et al. [34], The aryl bromide, 6-amino-7-bromo-5,8-dimethylisoquinoline (45) was derived from 2,5-dimethylanilinc in nine steps. The Suzuki coupling of 45 with phenylboronic acid was carried out using catalytic tetrakis(triphenylphosphine)palladium in benzene and with Na,CO, serving as the base to furnish... 

In the total synthesis of naturally occurring indole alkaloids, applications of n-allylpalladium intermediate and C-N bond formation are developing areas (126]. With the advent of new methodologies in these fields, especially with the successes of the Buchwald and Hartwig s chemistry, more syntheses using those strategies are to be expected. 

Chapter 3 by Jie Jack Li presents a collection of very interesting total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. Five different types of palladium-mediated reactions are treated (I) oxidative cyclization reactions promoted by palladium (II) species (2) transmetallation reactions with organoboranes, organoslannanes, and organozinc reagents (3) inter- and intramolecular Heck reactions (4) reactions with it-allylpalladium as the intermediate and (5) reactions using C-N bond formation as the key step for the synthesis. 

F. Puisieux, R. Goutarel, M.-M. Janot, and A. Le Hir, Compt. rend., 1956, 242, 2981. As far as is known, all naturally occurring indole alkaloids possessing the ethylidene or hydroxy-ethylidene side chains have the geometric configuration shown [C(19)-Me cis to C(15)]. = ... 

The tetracyclic oxindole alkaloids possess four asymmetric centers (C-3, C-7, C-15, and C-20) and therefore can exist as sixteen possible diastereoisomers. However, since all naturally occurring indole alkaloids of the corynane type possess a C-15a hydrogen [17), the total number of isomers is restricted to eight. Taking into consideration the asymmetric... 

Reduced [l]benzothieno[2,3-c]pyridines (109) are of potential biological interest because the 3-CH2CH2N — side chain just described is now constrained in a ring, and of chemical interest as useful precursors of sulfur analogs of naturally occurring indole alkaloids. 

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