Tetramethyleneglutaric acid

Product studies in certain buffers of various concentrations furthermore demonstrate that the decomposition of the neutral tetrahedral intermediate TH from N-phenyliminotetrahydrofuran to aniline and butyrolactone, is general acid-base catalyzed (without affecting the rate of disappearance of the substrate) (Cunningham and Schmir, 1966). Effective buffers are acetate, phosphate, bicarbonate, arsenate, phenyl-phosphate, and 3,3-tetramethyleneglutaric acid ineffective buffers are tris-(hydroxymethyl)-aminomethane, imidazole andp-nitrophenol. The capability of the effective buffers, which are all bifunctional, can be attributed to a cyclic internal acid-base catalyzed decomposition of the neutral intermediate TH (transition state 16). 

The development of aldose reductase inhibitors began in 1967, when tetramethyleneglutaric acid (TMG) was introduced as the first non-cytotoxic inhibitor of aldose reductase in experimental models (Kinoshita et al., 1968). Of more than a hundred potential aldose reductase inhibitors with in vitro... 

Tetramethyleneglutaric acid (TMG) (62) and alrestatin (AY-22,284) (63)) are known aldose reductase inhibitors. From natural products, a number of flavonoids have been reported to have aldose reductase inhibitory activity. Quercetin (64 1, R = H), quercitrin (64 2, R = L-rhamnose), rutin (64 3, R = rutinose (6-O-a -L-rhamnosyl-D-glucose)) and myricitrin (65 2, R = L-rhamnose) were much more effective inhibitors of aldose reductase from rat lens than TMG (62) and alrestatin (63) [66]. Quercetin with 3, 4 -dihydroxy substitution in ring C was more potent... 

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