Natural lamellarins

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

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

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. 

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... 

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... 

Another interesting investigation of the use of microwave irradiation for the synthesis of alkaloids was recently reported by M. Alvarez et al., where the authors investigated a modular total synthesis of Lamellarin D [93]. After 20 years of the first isolation of this compound from the marine prosobranch mollusk Lamellaria sp, this family currently comprises more than 30 members, isolated from various natural sources. With its recent identification as... 

Treatment of the dihydroisoquinolinium salt 699 with Hiinig s base (/-PrzNEt) produces the corresponding azomethine ylide, which can undergo intramolecular cycloaddition with the tethered alkyne to afford the chro-meno[3,4- ]pyrrol-4(3//)-one 700 in high yield. Subsequent deprotection of the isopropyl protecting groups affords the marine natural product lamellarin K (Scheme 173) <1997CC2259>. 

A new synthetic approach to pyrrolo[2,l-a]isoquinolines, important moieties found in natural products (e.g., lamellarins), has been reported <07S1003>. /V-Alkylation of Bischler-Napieralski derived isoquinolines with ethyl bromoacetate gave the corresponding quaternary... 

Heating of the dihydroisoquinoline 285 with the nitrostyrene 286 allowed practical preparation of the system 287 en route to the natural product lamellarin K <2004AGE866>. Reactions between nitroalkenes and enaminones have also been employed as the key step in a solid-phase approach to pyrrole-3-carboxamide derivatives (Equation 88) <1998TL8263>. 

The lamellarins constitute an important group of natural products isolated from marine invertebrates such as sponges, molluscs and tunicates with structures without precedents in natural or synthetic compounds. They are characterized for possessing important biological activities. The aim of this review is to provide an overview of the work published since the isolation of the first group of lamellarins <85JA5492> from the marine prosobranch mollusc Lamellaria sp, imtil the beginning of 2004. 

Following on from their previous work on the biomimetic synthesis of marine natural products, Steglich et al. proposed a biomimetic lamellarin synthesis in which an oxidative dimerization of an arylpyruvic acid and condensation of the resulting 1,4-dicarbonyl compound with a suitable 2-arylethylamine would be the key steps of the synthesis. Thus, the synthesis of lamellarin G trimethyl ether was achieved by coupling two molecules of 3-(3,4-dimethoxyphenyl)pyruvic acid and the appropriate 2-phenylethylamine <9579941, 97AG(E)155>. The use of a mixture of two different arylpyruvic acids afforded the unsymmetrical lamellarin L <00MI1147>. 

Investigation of animals from the marine enviroiunent has thrown up an intriguing variety of poly-heterocyclic products (sometimes called sea alkaloids) five representatives are variolin B (sponge, Kirkpatrickia varialosa), lamellarin B (mollusc, Lamellaria sp.), ascididemine (mnicate, Didemnum sp.), wakayin ° (ascidian, Clavelina sp.) and dendrodoine" (tunicate, Dendroda grossular), a rare natural example of a multi-heteroatom compound. 

During the past few years, the polyoxygenated 2,3,4-triarylpyrrole natural products known collectively as the lamellarins have been amongst the most thoroughly studied class of natural products. An interesting cyclocondensation reaction between imine 1 and nitroalkene ester 2 led to highly functionalized pyrrole ester 3, an intermediate which was converted to lamellarin L <04AG(E)866>. A similar reaction with a nitrocoumarin Michael acceptor proved to be less effective. 

Lamellarin-20-sulfate The screening of diverse marine natural products for compounds active against integrase... 

Chittchang, M., Gleeson, M. P., Ploypradith, P., Ruchirawat, S., (2010). Assessing the drug-likeness of lamellarins, a marine-derived natural product class with diverse oncological activities. Eur. J. Med. Chem. 45, 2165-2172. 

A method for the direct C3 arylation of pyrroles 68 was developed with the goal of achieving the total synthesis of the lamellarin family of natural products 71. This -selective C-H arylation of pyrroles has a broad scope and is amenable to complex molecule synthesis (14JA13226). 

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