Pyrrole, alkaloid synthesis from

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

Peramine (352) is a pyrrole alkaloid identified as a major insect feeding deterrent isolated from perennial ryegrass infected with the entophyte Acre-monium lolii. Due to the interesting heterocyclic ring system and biological activity, the synthesis of peramine is attractive [230],... 

In addition to furan, other heterocycles have been examined." Thiophene undergoes efficient photocycloaddition with benzaldehyde to afford a single exo photoproduct (183) in 60% yield. As reported by Jones and coworkers,the photolysis of IV-methylpyrrole in the presence of aldehydes or ketones yields the corresponding 3-hydroxyalkyl derivative (184), even when the reaction mixture is free from any trace of acid. In order to use the pyrrole nucleus for stereoselective alkaloid synthesis (cf. caesalpinine, 185) in the fashion developed with the furan nucleus, pyrrole substituents that stabilize the presumed intermediate bicyclic oxetane must be discovered. 

During a synthesis of lamellarin and related pyrrole alkaloids, Iwao et al. observed the Pd(OAc)2-mediated decarboxylative cyclization of pyrrole acid 52 to 53 [44]. Lesser amounts (12%) of the product from decarboxylation of 52 were isolated. 

Breckle, G Polborn, K., and Lindel, T. (2003) Synthesis of the pyrrole-imidazole alkaloid sventrin from the marine sponge Agdas svmtres. Z. Natuiforsch. B Chem. Sci., 58,451-456. 

Two new polycyclic pyridoacridine alkaloids, arnoamine B, 289, and its demethylated analogue, arnoamine A, have been isolated from the ascidian Cystodytes sp. These new compounds are the first known examples of pyrroles fused to pyridoacridines, have antifungal properties, and are cytotoxic in several human tumor cell lines <1998JOC1657>. Both these compounds have been synthesized, starting from the hydrazone 290 with a Fischer indole synthesis (Scheme 73) <2000JOC5476>. 

The Aspidosperma family of indole alkaloids has inspired many synthetic strategies for the construction of their pentacyclic framework of the parent compound aspidospermidine (366), since the initial clinical success of two derivatives, vinblastine (10) and vincristine, as anticancer agents. The alkaloids such as (-)-rhazinal (369) and (-)-rhazinilam (6) have been identified as novel leads for the development of new generation anticancer agents [10,11]. Bis-lactams (-)-leucunolam (370) and (-t-)-epi-leucunolam (371) have bio-genetic and structural relationships with these compounds [236]. Recently, enantioselective or racemic total syntheses of some of the these natural product were achieved. One successful synthesis was the preparation of the tricyclic ketone 365, an advanced intermediate in the synthesis of aspidospermidine (366), from pyrrole (1) (Scheme 76) [14]. The key step is the construction of the indolizidine 360, which represents the first example of the equivalent intramolecular Michael addition process [14,237,238]. The DIBAL-H mediated reduction product was subject to mesylation under the Crossland-... 

We move from benzo-fused pyrroles to benzo-fused pyridines and meet quinoline and isoquinolinc. Isoquinolines will feature as benzyl isoquinoline alkaloids in Chapter 51 and their synthesis will mostly be discussed there. In this section we shall concentrate on the quinolines. 

Using another approach, starting from the pyrrole core <04TL0000> syntheses of lamellarins Q and O were also achieved. In this work, the methyl A -(triisopropylsilyl)-3,4-dibromopyrrole-2-carboxylate 102 was used as the initial scaffold. Banwell et al. <97CC207> used the dibromopyrrole 102 in an elegant convergent synthesis of several compounds from this family of marine alkaloids (shown above). 

However, the following are examples of direct electrophilic alkylation of imidazole. A two-step synthesis of marine natural product ageladine A 271 started from the commercially available histamine 269 and the pyrrole-2-carbox-aldehyde 268. The entire skeleton of the alkaloid was built in one step via a Pictet-Spengler type condensation. The reaction was accelerated by Lewis acid scandium triflate, although the reaction did proceed without a catalyst but at a slower pace (Scheme 68) <20060L4083>. 

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