5- Methyl-3-pyrrolin-2-one

Jatropham (surely better called jatrophine) is an alkaloid occurring in Jatropha macrorhiza (Euphorbiaceae) which has inhibitory activity towards leukaemia. Its racemic form (4) has been synthesized from 3-methyl-2-furoic acid, as outlined in Scheme l.5 This synthesis vindicates an earlier suggestion that the structure be revised to 5-hydroxy-3-methyl-3-pyrrolin-2-one (4), as opposed to the 4-methyl isomer.6... 

The phosphonate unit [164] was prepared by bromination of N-Boc-3-methyl-3-pyrrolin-2-one [165] with NBS followed by reaction with neat triethyl phosphite. Deprotonation with sodium hydride and reaction with the above mentioned carbaldehyde led to the exclusive formation of N-Boc-ampullicin. Final deprotection gave (-)-ampullicin (91a). (+)-Isoampullicin (91b) is obtained by isomerization with iodine (Scheme 44). 

Heterocyclic stannanes were also employed and yielded 5-acetoxyfuran-2(S/f)-ones and S-acetoxy-1-methyl-3-pyrrolin-2-one from 2-stannylfrirans and 2-stannyl- -methylpyrrole. respectively (Scheme... 

Heterocyclic stannanes were also employed and yielded S-acetoxyfuran-2(S//)-ones and S-acetoxy-1-methyl-3-pyrrolin-2-one from 2-stannylfi s and 2-stannyl-A(-methylpyrTole, respectively (Scheme 8). In the furan system, it appears initial oxidation of the stannane provides the 2-furyl acetate, which is known to undergo further oxidation with LTA (Scheme 8). ... 

Ultrasound irradiation of mixtures of amines RNH2 (R = PI1CH2, Ph or Ar) and methyl pyruvate results in the 3-pyrrolin-2-ones 322377. The silver tetrafluoroborate-catalysed cyclization of the allenic amines 323 leads either to a pyrroline 324 or tetrahydropyridine 325, depending on the structure of the amine. The former is formed from 323 (R = H), the latter from 323 (R = Me)378. 

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. 

A soln. of 3-acetylamino-l-methyl-4-benzylthio-5-benzylthiomethyl-3-pyrrolin-2-one and diloranil in benzene refluxed 0.5 hr. 3-acetylamino-l-methyl-4-benzyl-thio-5-benzylthiomethylene-3-pyrrolin-2-one. Y 82%. F. e., also with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone, s. K. Hagio and N. Yoneda, Chem. Ind. 1974, 494 thiophenes from 2,5-dihydrothiophenes s. J. M. McIntosh and H. Khalil, Can. J. Chem. 53, 209 (1975) thioenol- from thio-ethers with sulfuryl chloride s. S. Iriudiijima et al., Agr. Biol. Chem. (Tokyo) 40, 1031 (1976). 

An intramolecular Pd-mediated Heck-type approach to 3-pyrrolin-2-ones has been disclosed by Yang and Shea (1995MI1 Scheme 30). Treatment of N-allyl-2-bromoacetamide 152 with palladium acetate and triphenylphos-phine in acetonitrile gives 4-methyl-3-pyrrolin-2-one 153 by a 5-exo-trig cyclization onto a terminal alkene, reductive elimination, and isomerization... 

Prandi and coworkers investigated cychzation reactions involving dien-amides they found differential reactivity based on the substitution pattern of the dienamide (Scheme 48 2011OBC2535). For example, treatment of dienamide 211 with TFA led to the formation of 3-pyrrolin-2-one 212. The same reaction with the methyl-containing substrate 213 led to the formation ofimino ether 214. The structures of the 3-pyrrolin-2-one products were confirmed by ROESY NMR experiments the structure of one of the imino ether products (N-naphthyl) was confirmed by single crystal X-ray analysis. 

Kurahashi and Matsubara have used an isocyanate as both a nitrogen source and CO equivalent in a [24-2+1] cycloaddition to give 3-pyrrolin-2-ones (Scheme 110 2010CC8055). Mixing methyl acrylate (415), 2-octyne (416), and phenyl isocyanate (417) with a Ni catalyst and carbene hgand gives a 5 1 mixture of the 3-pyrrolin-2-ones 418 and 419, respectively. 

Tetramic acid derivatives have been converted into 4-unsubstituted 3-pyrrolin-2-ones utilizing a two-step procedure developed by Decicco and Glover (Scheme 136 1996JOC3534). Reduction of tetramic acid 495 with sodium borohydride gives the 4-hydroxypyrrohdine 496 elimination of the mesylate derived from 496 then gives 5-methyl-3-pyrrolin-2-one 497. Compound 497 is a building block used en route for a total... 

Padwa and coworkers realized the synthesis of 2,4-disubstituted pyrroles using rearrangements of 2-fiiranyl carbamates via 5-methoxy-3-pyrrolin-2-one intermediates. 2-Furanyl carbamate 593 was treated with iodine and sodium bicarbonate followed by methyl iodide and silver oxide to give the N-substituted 5-methoxy-3-pyrrolin-2-one 595 via the iodinated intermediate 594 (Scheme 173 20090L1233). Padwa employed this method to synthesize 5-methoxypyrrol-2-ones, which were then treated with alkyl hthiates to give tricycHc products (2009T6720). 

It is interesting to note that 4-aminopent-3-en-2-one (85), which is held in a cisoid arrangement by hydrogen bonding, gives the product 86, which is stable in anhydrous solvent, but which cyclizes under the influence of water to give methyl 2-methyl-5-oxo-4-(2-oxopropylidene)-2-pyrroline-3-carboxylate (87). 

Figure 16. Oligo(pyrrolinone) backbones linked through the 2,5- and 3,5-positions. The correlation between the 3,5-linked pyrrolin-4-ones and a-peptide /3-strands. The S(6) hydrogen-bonding interaction is indicated in red. TV Methylated 3,5-linked pyrrolin-4-one sequence 1 adopts a helical conformation in the solid state and in solution.

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