Pyridones continued

TABLE XIM2. Alkyloxy, Aryloxy, and Hydroxy 2-Pyridones (Continued)... 

TABLE XI-124. Dihydro-2-pyridinolsand Dihydro-2-pyridones(Continued)... 

Continued efforts to improve the activity of the monobactams against nonfermenting gram-negative rods such as Pseudomonas aeruginosa led to the discovery of SQ 83,360 [104393-00-2] (58), C22H24N q0 2 2 3-hydroxy-4-pyridone containing monocarbam. The enhanced activity of SQ 83,360 is... 

Work under this classification (76AHCS1, p. 31) continues to be sparse. Heat-of-solution data provide a useful method for estimating A// for tautomeric processes in nonaqueous solvents, as was illustrated in the case of 2-pyridone 15a/2-hydroxypyridine 15b equilibrium (76TL2685). Heats of dehydration of 4-hydroxypyrazolines into pyrazoles and 5-hydroxyisoxazolines... 

In the second instance, two approaches seem to be worthy of special note. The synthetic utility of elemental phosphorus based on it acting as a radical trap appears to be quite valuable, but additional effort is required to determine the variability of the source of the organic free radicals. (Is there some other, more efficacious, source of organic free radicals that works better with this system than acylated iV-hydroxy-2-pyridones ) The other approach that appears ripe for development is the hydrolysis/elimination with "phosphorates" derived from the oxidative addition of white phosphorus to alkenes. We look forward to the continued development of such facile approaches toward the preparation of fundamental phosphonic acids. 

N-Hydroxythiopyridone is purchased from the Olin Corp. as an aqueous 40% solution of sodium 2-pyridinethiol-1-oxide (sodium omadine). Sodium omadine (1 L) is diluted with water (H2O, 600 mL) and the solution cooled to 0°C. Hydrochloric acid (350 mL) is added dropwise over a 20-min interval with continuous stirring and cooling for a further 20 min. The resulting suspension containing N-hydroxythio-pyridone is filtered and the solid is washed with H2O (2 L). The N-hydroxythiopyridone is dried over sodium hydroxide or potassium hydroxide under reduced pressure and... 

Cavalleri et al. (219) studied the cycloaddition of thioisomiinchnones with 5-amino-4-methylene-l,2,3-triazolines. The resulting cycloadducts afford 2-pyridones with Raney Ni or 8-thia-6-azabicyclo[3.2.1]octanes with acid. Kato has continued his extensive exploration of cycloaddition studies of mesoionic heterocycles with atypical dipolarophiles. Thus, whereas thioisomiinchnone (320) gave a complex mixture with 6,6-dimethylfulvene (119), it reacted with 2-tert-butyl-6,6-dimethylfulvene to afford 321 in 17% yield (151,152). The cycloaddition of 320 with benzocyclobutadiene was much cleaner to give 322 in 70% yield (114). 

In fact, it isn t necessary to make 57 as, when R=Me, it is the natural alkaloid arecoline. However, when the synthesis was continued by attempted conjugate addition of the enolate of methyl acetoacetate to 57 only very low yields (12-18%) of products could be found. The problem turned out to be the base-catalysed rearrangement of 57 into the aromatic pyridone 71. 

The excretion of methyl pyridone carboxamide is more severely reduced in marginal niacin deficiency than is that of -methyl nicotinamide. The excretion of methyl pyridone carboxamide decreases rapidly in subjects fed on a niacin-deficient diet, and virtually ceases several weeks before the appearance of clinical signs of deficiency by contrast, a number of studies have shown continuing excretion of -methyl nicotinamide even in pellagrins. A better estimate of niacin nutritional status can be obtained by determining the ratio of urinary methyl pyridone carboxamide Ai -methyl nicotinamide, which is relatively constant, despite the administration of loading doses of tryptophan or niacin to adequately nourished subjects (between 1.3 to 4.0), and a ratio of less than 1.0 indicates depletion of niacin reserves (de Eange and Joubert, 1964 Dillon et al., 1992). 

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