Pentobarbital, synthesis

Thiourea (H2NCNH2) reacts with diethyl malonate and its alkyl derivatives in the same way that urea does Give the structure of the product obtained when thiourea is used instead of urea in the synthesis of pentobarbital The anesthetic thiopental (Pentothal) sodium is the sodium salt of this product yWhat IS the structure of this compound ... 

The last step in the synthesis of pentobarbital is the reaction of the appropriately substituted derivative of diethyl malonate with urea. 

Castilho et al. (1990) studied the intestinal mucosal cholesterol synthesis in rats using a chronic bile duct-ureter fistula model. Male Wistar rats weighing 300-350 g were anesthetized with 50 mg/kg pentobarbital i.p. and submitted to a bile duct-right ureter fistula utilizing a PE-50 catheter after a right-kidney nephrectomy. 

A series of other barbiturates (phenobarbital, barbital, thiopental, pentobarbital at 1 mmol l i concentration inhibit the orotate uptake system without affecting the incorporation of uracil into cellular pyrimidines [287]. While barbituric acid and hexobarbital are less active, phenylethylhydan-toin, chlorpromazine and phenethyl alcohol are extremely active. Phenobarbital also depresses the utilization of orotic acid for the synthesis of cytidine nucleotides in the liver [288]. a-Hexachlorocyclohexane, an inhibitor of the phenobarbital type, was even more effective in depressing de novo cytidine nucleotide synthesis from orotic acid [289]. 

As xanthine oxidase activity has been demonstrated to occur in the rat kidney but not in monkeys 5) the net secretion observed in rat proximal tubules could be due to cellular rather than to transtubular secretion. The influence of urate synthesis on urate excretion was studied by clearance methods in rats anesthetized with pentobarbital. The animals were infused with hypoxan-thine (0.5 ug/min)a metabolic precursor of urate, or allopurinol, (5 ug/min), a xanthine-oxidase inhibitor. 

The synthesis of barbiturates is relatively simple and relies on reactions that are now familiar enolate alkylations and nucleophilic acyl substitutions. Starting with diethyl malonate, or malonic ester, alkylation of the corresponding enolate ion with simple alkyl halides provides a wealth of different disubstituted malonic esters. Reaction with urea, (H2N)2C=0, then gives the product barbiturates by a twofold nucleophilic acyl substitution reaction of the ester groups with the -NH2 groups of urea (Figure 22.7). Amobarbi-tal (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal) are typical examples. 

---