Succinimide ring opening

Condensation of allyl isocyanate with succinimide affords the cyclic diacylurea 39. Acid hydrolysis leads to ring opening of the succinimide (40). Oxymercuration of the terminal olefin bond with mercuric acetate in methanol solution affords the diuretic meralluride (41). ... 

The cyclized analog of meralluride is prepared by a similar synthesis. Thus, condensation of camphoric acid (42) (obtained by oxidation of camphor) with ammonia gives the bicyclic succinimide (44). Reaction with allyl isocyanate followed by ring opening and then reaction with mercuric acetate affords the mercury derivative (45) as the acetate rather than the hydroxide as above. Reaction with sodium chloride converts that acetate to the halide (46). Displacement on mercury with the disodium salt of thioglycollic acid affords the diuretic mercaptomerine (47). ... 

You and co-workers have demonstrated a further application of NHCs in the kinetic resolution of formyl p-lactams ( )-265 [103]. Upon treatment with a chiral NHC, the Breslow-type intermediate is formed, followed by ring-opening of the P-lactam moiety, with subsequent trapping of the acylazolium intermediate leading to the enantio-enriched succinimide product 266 and resolved formyl P-lactam (which is reduced to its alcohol 267). The authors note that when R" = H, the products undergo racemisation readily, and this is a possible explanation for the lower levels of enantioselectivity observed in the succinimide products 266 (Scheme 12.60). 

Our next examples concern ring-substituted succinimides. 2-Phenylsuc-cinimide (4.185), the A-demethylated metabolite of the antiepileptic drug phensuximide, was found to be a better substrate of DHPase than succinimide itself. Two ring-opened metabolites are conceivable, 3-phenylsuccin-amic acid (4.186) and 2-phenylsuccinamic acid (4.187), but only the latter was formed enzymatically. 2-Phenylsuccinimide is chiral, and ring-opening... 

Considering now glutarimide derivatives, we find that 2-phenylglutari-mide (4.196, R=H) was not a substrate for the partially purified rat liver DHPase, in contrast to glutarimide itself [114][123], Thus, here, the introduction of the Ph group had the opposite effect than in succinimide derivatives. Similarly, no ring-opened metabolite of glutethimide (4.196, R=Et) was found either in vitro or in vivo [124],... 

The most important degradation mechanism of asparagine and glutamine residues is formation of an intermediate succinimidyl peptide (6.63) without direct backbone cleavage (Fig. 6.29, Pathway e). The reaction, which occurs only in neutral and alkaline media, begins with a nucleophilic attack of the C-neighboring N-atom at the carbonyl C-atom of the Asn side chain (slow step). The succinimide ring epimerizes easily and opens by hydrolysis (fast step), as shown in Fig. 6.27, to yield the iso-aspartyl peptide (6.64) and the aspartyl peptide (6.65) in a ratio of 3 1. 

Bicyclic cyclopropanone aminals with a succinimido moiety as iV-substituent allow displacement of succinimide by hydrogen by heating with triethylammonium formate giving 1. A ratio 3 1 of formate to aminal gave the best results. This reduction could not be applied to bicy-clo[3,1.0]hexane or bicyclo[9.1.0]dodecane systems due to ring-opening reactions under these conditions. ... 

The rate of ring closure is a function of the sequence it is fast if R = H, that is in peptides containing the — Asp-Gly — partial sequence and orders of magnitude slower if the aspartyl residue is followed by an amino acid with a bulky side chain, such as valine (R = isopropyl). Opening of the succinimide ring with alkali is not helpful because )8-aspartyl peptides are produced as the preponderant product ... 

We used a synthetic polypeptide, a,P-poly[N-(2-hydroxyethyl)-D,L-aspartamide], which was prepared by aminolysis with aminoethanol of D,L-poly uccinimide obtained by thermal polycondensation The polysuccinimide is fully racemic and the aminolysis results in random opening of the succinimide rings, as demonstrated by the C-NMR spectrum As enzymes hydrolyze only the peptide bond... 

Thermolysis of A-acetylpropanamide (93) has been investigated using a hybrid d-functional theory (DFT) B3LYP method and shown to occur by two mechanisms, methyl-proton transfer and methylene-proton transfer, the activation barrier for the former being lower than that of the latter. A review (37 references) of recent examples of ring-opening reactions of succinimides (94) has covered alcoholysis, aminolysis, and reactions with carbon nucleophiles. ... 

On the other hand, several nucleophilic reagents and catalysts have been found capable of promoting the ring expansion of 4-formyl p-lactams, and/or their imine derivatives, to afford open chain acyl thiazole or succinimide derivatives. For example, treatment of 4-formyl p-lactam 199 with 2-(trimethylsilyl)thiazole,... 

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