Pukeleimides

Marine organisms have provided very complex molecules possessing a pyr-rolidinone ring as part of a urea function dysidin (105) (140), malyngamide A (106) (141) and pukeleimides A, B, C, D, E, F, and G (107-113) (142, 143). 

From another shallow-water variety of L majuscula found in Hawaii, a new crystalline metabolite pukeleimide C (102) was isolated. The structure was secured by X-ray studies [163]. Chiroptical studies showed the compound to be racemic and, probably, an artefact. A separate collection of the cyanophyte did not contain pukeleimide C but, instead, yielded a group of related metabolites, e.g. 103, whose structures were assigned from spectral data [164], Unfortunately, no information is available on the bioactivity of these metabolites. 

Other types of tetramic acid derivatives are A-acyl-4-methoxy-3-pyrrolin-2-ones or 4-O-methyl ethers of A-acylated tetramic acids. The only metabolites of this type containing a dienic structure are pukeleimides A (87), G (88), B (89) and F (90). They are nontoxic compounds isolated from the marine cyanophyte Lyngbya majuscula [158], a blue-green algae. 

Only the total synthesis of pukeleimide A (87) has been described [159]. The strategy is based on the Wittig olefination of a substituted maleimide to give the ester (A) and on the reduction of 3-methoxymaleimide to give the pyrrolone (B). 

Compound (A) was transformed into its acyl chloride and reaction with (B) gave the precursor of pukeleimide A. The latter was oxidized with selenium dioxide to give the expected product (87) (Scheme 41). 

The synthesis of 5-ylidenepyrrol-2(5H)-ones (266) from the reaction of maleimides with stabilised phosphoranes under vigorous conditions has been reported.Attempts to use similar reactions of unstabilised phosphoranes, phosphonate-, or phosphine oxide carbanions led to intractable products or recovered starting materials. The procedure developed in these studies has been applied to the synthesis of pukeleimide A (269) using the formation of the ylidenepyrrolone (268) from the maleimide (267) as a key step. ... 

Several new pyrrolinones have been encountered in marine sources. Malyn-gamide-A, for example, is a chlorine-containing metabolite of the blue-green alga Lyngbya majuscula Gomont. Structure (7) has been proposed chiefly on the basis of n.m.r. and mass spectral analysis, aided by some chemical transformations. Seven other compounds, the pukeleimides A, B, C, D, E, F, and G, have also been isolated from the same source, and separated. They are formulated as (8), (9), (10), (11), (12), (13), and (14) as a consequence of spectral and, in the case of C, X-ray diffraction analysis. ... 

Danger and co-workers used an acid-catalyzed Dimroth rearrangement to prepare. /V-aryl-5-alkylildene-2,5-dihydropyrrol-2-ones. These eompounds are potent inhibitors of serine proteases, and are important intermediates in synthesis of y-laetams and tetramie aeid antibiotics such as pukeleimid A. Treatment of fiiran 100 in THF with and without the presence of lithium chloride gave the eorresponding a,P-unsaturated ketone 101 in 56% and 12% yield, respeetively, illustrating the importance of the acid catalyst for this system. 

C13H26CIN, Pumiliotoxin C hydrochloride, 43B, 746 C14H8N2O2 H2O, Amarorine monohydrate, 46B 575 C14H18INO2, Phyllochrysine methiodide, 31B, 240 C14H18N2O6, Pukeleimide C, 45B, 627... 

Haase and Langer employed a similar approach in the formal synthesis of pukeleimide A (2005SL453). 5-Alkyhdene-substituted fiiran-2-one 587 stirred with ammonium acetate and acetic acid provides the corresponding 3-pyrrohn-2-ones 588 and 589 as a separable mixture of E/Z isomers (Scheme 171). In 2009, Haase and Langer showed more examples of this chemistry using 5-alkyUdene-substituted furan-2-ones and alkyl- or arylamines. The ratio of E/Z-isomers is dependent on N-substitution (2009T4530). 

Simmons, C.J., Mamer, F.J., Cardellina, J.H., and Moore, R.E. (1979) Pukeleimide C, a novel pyrrolic compoimd from the marine cyanophyta Lyn ya majuscula. Tetrahedron Lett., 20,2003-2006. 

James, G.D., Mills, S.D., and Pattenden, G. (1993) Total synthesis of pukeleimide A, a 5-ylidenepyrrol-2(5 H)-one from blue green algae. J. Chem. Soc. Perkin Trans. I, 2581-2584. 

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