Lamellarins

The pyrrole ring in numerous natural products has been constructed using a PK synthesis. Examples include lamellarin L, funebrine, magnolamide, and... 

Following the communcation in 2004, a full report appeared that described type Ilac cyclocondensation reactions between dihydroisoquinolines and a-nitrocinnamates leading to complex fused pyrroles <06JOC9440>. The latter were converted into the lamellarin alkaloids and related analogues. 

Type Ilbd pyrrole syntheses fall into three general categories (1) Hinsberg-type (2) azomethine ylide cycloadditions and (3) isocyanide-based cyclocondensations. The Hinsberg pyrrole synthesis, the cyclocondensation between iminodiacetates and oxalates, has been further exploited in the total synthesis of the lamellarins <06T594,06TL3755>. 

The Paal-Knorr reaction was also employed by Steglich in likely biomimetic approaches to the marine alkaloids lamellarin L <00CEJ1147> as well as purpurone and ningalin C <00TL9477>. The overall approach employed herein involved initial oxidative coupling of two arylpyruvic acids followed by condensation of the resulting 1,4-diketones with suitable... 

In 1997, Steglich reported (Scheme 7) the synthesis [29] of lamellarin G trimethyl ether (36) based on the biosynthetic proposal that such compounds arise from 3,4-dihydroxyphenylalanine (DOPA) secondary metabolites. 

Ishibashi and coworkers [26] have reported a very efficient method for synthesizing a variety of lamellarin alkaloids and the preparation of lamellarin D and H are presented in Scheme 8. 

Scheme 7 Steglich Group Synthesis of Lamellarin Natural Products...

Banwell s group has provided an alternative strategy [32] for obtaining the lamellarin framework and it is presented in Scheme 10. The methodology involves the formation of a 2,4-disubstituted pyrrole (53) containing an acid... 

Ruchirawat has also been active in the construction of the lamellarins and his route [33] to lamellarin G trimethyl ether (36) is depicted in Scheme 11. 

In this route a dihydroisoquinoline (58) is N alkylated with a highly functionalized o -bromoacetophenone (59) to give a quaternary salt (60), which is treated with base and cyclizes to a pyrroloisoquinoline (60). The pyrrole nucleus is then formylated under Vilsmeier-Haack conditions at position 5 and a proximate mesylated phenolic group is deprotected with base to yield a pen-tasubstituted pyrrole (61). Subsequent oxidative cyclization of this formylpyr-role produces the 5-lactone portion of lamellarin G trimethyl ether (36). This sequence allows for rapid and efficient analog synthesis as well as the synthesis of the natural product. 

Ishibashi and Iwao have reported [37] a novel route (Scheme 13) to lamellarin G trimethyl ether that utilizes a much different strategy than the one outlined in Scheme 8. The synthesis begins with the dialkylation of a phenethyl amine with ethyl a-bromoacetate to yield an aminodiester (67). 

Handy and coworkers [38] have also offered a very useful approach (Scheme 14) to lamellarin G trimethyl ether (36) and they have referred to this strategy as being modular in nature . The route starts with an N-protected 4-bromo-2-carboethoxypyrrole (72) and involves introduction of three different aryl groups via three sequential, regiospecific halogenations, which are... 

Davis, R.A. Carroll, A.R. Pierens, G.K. Quinn, R.J. (1999A)New lamellarin alkaloids from the Australian ascidian, Didemnum chartaceum. J. Nat. Prod., 62, 419-24. 

Boger has reported efficient total syntheses of the marine alkaloids ningalin A, lamellarin O, lukianol A, and stomiamide A each of which possess a common 3,4-diaryl-substituted pyrrole nucleus bearing 2- or 2,5-carboxylates <99JA54>. A key step in each of these syntheses utilized a zinc mediated reductive ring contraction of 1,2-diazines such as 29 to pyrrole 30, a precursor in... 

Banwell has developed a new approach to the core associated with several members of the lamellarin class of marine natural products. This approach utilized some interesting pyrrole arylation reactions including a Negishi. cross coupling of the iodopyrrole 46 followed by a double-barrelled Heck cyclization of the resultant arylpyrrole 47 yielding the core structure 48... 

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