Pyrrolidine-2, 4-diones

A total synthesis of (+/—)-gephyrotoxin started with the pyrrolidine-2,4-dione 161 which upon treatment with ethoxyacetylene magnesium chloride followed by dilute HCl gave the acrylate derivative 162. Subsequent reduction and treatment with phenoxyformyl chloride afforded 163. 

FIGURE 7.23 Decomposition of a Boc-amino-acid /V-carboxyanhydnde by tertiary amine. Two molecules combine with the release of two molecules of C02 to form a pyrrolidine-2,4-dione. 

C Pothion, J-A Fehrentz, A Aumelas, A Loffet, J Martinez. Synthesis of pyrrolidine-2,4-diones from urethane N-carboxyanhydridess (UNCAs). Tetrahedron Lett 37, 1027, 1996. 

Boron trifluoride-mediated acylation of pyrrolidine-2,4-dione 68 led to the isolation of the neutral boron difluoride complex 2, which was sufficiently stable to be purified by column chromatography (Equation 18). This compound has been characterized crystallographically as noted above <1990J(P1)1959>. 

The neurotoxic lipophilic tripeptide, janolusimide (112), was isolated from the Mediterranean nudibranch Janolus cristatus. The structure was determined by spectroscopic and classical chemical methods [181] and confirmed by synthesis [182]. It has been suggested that the pyrrolidine-2,4-dione may arise from condensation of valine and isobutyrate [181]. 

The addition of an acetylenic ester to the anion derived from the pyrrolidine-2,4-dione 96 has been used by Lowe, Ridley, and Yeung115-118 in an elegant synthesis of /3-lactams related to the cephalosporins. Dibenzyl acetylenedicarboxylate gave a mixture of the fumarate (major product) and maleate (97), which could be separated by chromatography. Photolysis of the mixture in the presence of /-butylcarbazate gave the lactam 98, which was isolated only as the E-isomer. 

Recent developments in the use of organic costabilisers for stabilisation of PVC are reviewed, with particular attention to a new class of polyketones (pyrrolidine-2,4-diones) recently patented by Akcros Chemicals. The... 

In previous investigations by the author (2) and others (3), sulfonyl enaminone derivative of 2-[(2,4,6-trimethyl-3-(4-methyl-phenyl))-phenyl]-5,5-pentamethylene-pyrrolidine-2,4-dione (I) was prepared by reacting with methanesulphonyl chloride as illustrated in Eq. 3 ... 

Acylation of tetramic aclds. This Lewis acid is generally superior to BFs etherate or SnCU for acylation of tetramic acids (pyrrolidine-2,4-diones), particularly when the acyl group is unsaturated. An example is shown in equation (I). 

UNCAs are able to dimerize in the presence of some bases to yield pyrrolidine-2,4-diones, therefore the solvent and the base have to be chosen with care since, if the acylation step is slow, the risk of dimerization increases. This problem is not very important in solid-phase synthesis as the formed pyrrolidine-2,4-diones can be easily eliminated by the washing steps, but the concentration of reactive UNCAs can be drastically reduced by this phenomenon. No pyrrolidine-2,4-diones are formed when NMM is used as a base in di-chloromethane, DMF, and THF as solvents, while DIPEA in dichloromethane and DMF can yield this side-product. 

In this reaction, the formation of two series of compounds is proposed because in the chromatographic separations of polypeptide pyrolysates, an additional peak is noticed for each 3-alkenyl-5-alkyl-pyrrolidin-2,4-dione. This second peak is assigned to the corresponding 2,4-dialkyl-3,5-diketopyrroline (position isomers are not possible when R2 and R3 are identical) [1]. The list of different compounds from these two classes that may be formed during laser irradiation of different mammalian tissues [13a] due to peptide (protein) pyrolysis and the amino acid pair that can generate them is given in Table 12.2.3. 

Table 12.2.3. 3-Alkenyl-5-alkyl-pyrrolidin-2,4-diones and 2,4-dialkyl-3,5-diketopyrrolines that can be formed from laser pyrolysis of mammalian tissues [13a].

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