Alkaloids Parham cyclization

This reaction was initially developed by Parham in 1975 and extended primarily by Bradsher after Parham s death in 1976. It is the synthesis of aryl or heteroaryl ring fused carbocylces or heterocycles through the intramolecular reaction between a side chain electrophile and an aryl or heteroaryllithium generated from lithium-halogen exchange. Therefore, this reaction is generally known as the Parham cyclization. Occasionally, it is also referred to as the Parham reaction. J This reaction is very useful for the synthesis of alkaloids. ... 

In view of three excellent recent reviews on the Parham cyclization, " this section focuses mainly on the more recent literature. While -butyllithium and tert-butyllithium are commonly used to effect halogen-lithium exchange, these reagents do present problems as delineated earlier. Mesityllithium does not pose such problems since the resulting mesityl halides are not susceptible to the side reactions inherent with -butyl and tert-butyl halides. Mesityllithium has been used to prepare the camptothecin precursor 28. This base can also be used with added electrophiles, as for the conversion of 29 to phthalides 30. A more conventional Parham synthesis of phthalides, i.e., 31—>32, has been applied to the synthesis of the aristocularine alkaloids. ... 

Alkaloids that have been synthesized via a key Parham cyclization similar to 55— 56 include piperolactam C (57), goniopedaline (58), stigmalactam (59), nuevamine (60),cichorine (61), zinnimidine 62), fumaramidine (63), porritoxin (64), and vitedoamine A (65). ... 

The first syntheses of topoisomerase I inhibitors topopyrones B and C feature the cyclization of 84 to 85 albeit in low yield. Parham cyclizations onto both epoxides (e.g., 86— 87) and aziridines (e.g., 88—>89) are aspects of two approaches to pancratistatin and related alkaloids. ... 

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See also in sourсe #XX -- [ ]

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