Pentobarbital structure

Show by writing a suitable sequence of reactions how you could prepare pentobarbital from diethyl malonate (The structure of pentobar... 

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 ... 

Compounds of similar structure and ionization may have very different partition coefficients. For example, thiopental and pentobarbital are very similar in structure and acidity but have very different lipophilicity (Fig. 3.5), and hence their disposition in vivo is different (see below). 

Figure 3.5 Comparison of the structures and physicochemical characteristics of pentobarbital and thiopental.

These two molecules illustrate how subtle changes in molecular structure can affect action. Amobarbital requires 30 min to take effect and sedation lasts for 5-6 h, while pentobarbital takes effect in 15 min and sedation lasts only 2-3 h. Phenobarbital (R=ethyl, R =phenyl), on the other hand, requires over an hour to take effect, but sedation lasts for 6-10 h. When the alkyl chains are made much longer the sedative properties decrease and the substances become anticonvulsants, which are used to treat epileptic seizures. If the alkyl group is too long or is substituted at one of the two nitrogens, convulsants are produced. 

Weak acids and bases are often formulated as their salts to make them more water soluble. The ionised salts, however, do not cross biological membranes very well. Calculate the percentage of a dose of pentobarbital that will be ionised at plasma pH (7.4). The structure of pentobarbital is shown in Figure 1.8. 

The low concentration of protein in the interstitial fluid has been suggested as another factor which may reduce the distribution of some substances in the central nervous system. Lipid soluble compounds, such as methyl mercury which is toxic to the central nervous system (see Chapter 7). can enter the brain readily, the facility being reflected by the partition coefficient. Another example which illustrates the importance of the lipophilicity in the tissue distribution and duration of action of a foreign compound is afforded by a comparison of the drugs thiopental and pentobarbital (figure 3,5). These drugs are very similar in structure, only differing by one atom. Their pKa values are similar and consequently the... 

In moderate doses, the action of the benzodiazepines is remarkably like that of the barbiturates, but they are more selective because larger doses do not introduce the toxicity to the patient seen in barbiturate medication. Intravenous diazepam can be used in place of thiopental for the induction of general anaesthesia. It has been found that barbiturates act on the picrotoxin receptor in the GABA—receptor complex (Olsen, 1982) and, in this way, synergize the action of GABA. This effect is stereospecific for in pentobarbital it is confined to the (5)-isomer (Huang and Barker, 1980). It would seem that this type of activity plays only a minor part in medication with barbiturates which behave on the whole as structure-independent lipophiles (see p. 622). 

Figure 3 Mass spectra and chemical structures of pentobarbital (A) and methyl derivative of pentobarbital (B). (Reproduced with permission from Liu RH and Gadzala DE (1997) Handbook of Drug Analysis - Applications in Forensic and Clinical Laboratories, p. 225. Washington, DC American Chemical Society.)...

Fig. 230. Advanced intralysosomal degradation of unidentified structures and mitochondrial reoxygenation damage in a pinealocyte (block 1211) from a rat (No. 7) treated for 7 consecutive days with intraperitoneal injection of 1.5 ml Tyrode s solution per kg body weight x day. On the last 4 days of experimentation the animal was exposed to an atmosphere containing only 5 % oxygen for 30 min. Half an hour after the last exposure under pentobarbital anaesthesia (30 mg/kg), the animal was perfused from the abdominal aorta with 2.5 % glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4). Postfixation with 1 % osmium tetroxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Plate 3401...

The sesquiterpenes caryophyllene oxide (36) and p-selinene (= p-eudesmene) (37) isolated from the hexane extract from leaves of Psidium guajava var. minor Mattos (Myrtaceae) potentiated pentobarbital sleep and increased the latency for PTZ-induced convulsions in mice blockade of extracellular Ca was observed in isolated guinea-pig ileum with the hexane extract and its fractions containing both sesquiterpenes (Meckes et al. 1997). The similarity between the chemical structures of the sesquiterpenes (34), (35), and (37) is noteworthy and could indicate relevant characteristic patterns required for central activity. 

Draw structural formulas for the products of complete hydrolysis of meprobamate, phe-nobarbital, and pentobarbital in hot aqueous acid. 

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