Serotonin total synthesis

The asymmetric reductive ring opening of oxabenzonorbomene 53 was applied as a key step in the total synthesis of serotonin re-uptake inhibitor sertraline [77, 80]. 

C-A -Methylketanserin 279, the analogue of serotonin-2 receptor antagonist, ke-tanserin 280, has been synthesized for studying these receptors in vivo using PET by alkylation of ketanserin in DMF solution in the presence of small amount of aqueous tetrabutylammonium hydroxide at 80 °C for 2 minutes followed by chromatographic purification during 22 minutes total synthesis time from EOB, with 10% radiochemical yield calculated at the end of synthesis (EOS). 

The application of R. leads to a reduction in the levels of noradrenaline, dopamine, and serotonin in the synapses R. binds irreversibly to the transport system of noradrenaline (NA) so that the re-uptake of NA in the vesicles of the synapses is inhibited. Thus, transmission of stimuli is reduced, the blood pressure decreases with a concomitant central sedation. R. thus acts as a neuroleptic agent. The side effects of an overdose may include diarrhea, elevated secretion of saliva and gastric juices, depression, and Parkinson s disease. R. is suspected of being carcinogenic since in female patients an increased incidence of breast cancer seems to occur. The roots of R. serpentirm have been used in India for centuries as a sedative they also contain yohimbine. The first total synthesis was achieved by Woodward, for stereospecific synthesis, see Lit.. Deserpidine (11-demethoxyreserpine, canescine, recanescine, CsaHjgNjOg, Mr 578.64, cryst., mp. 228-230°C, [a]o-163° (pyridine) is also aRauvo/-fia alkaloid it exists in polymorphic forms and also lowers the blood pressure. 

Apart from the relatively small amounts that are required for synthesis of the neurotransmitter serotonin (5-hydroxytryptamine), and for net new protein synthesis, essentially the whole of the dietary intake of tryptophan is metabolized by way of the oxidative pathway shown in Figures 8.4 and 9.4, which provides both a mechanism for total catabolism by way of acetyl coenzyme A and a pathway for synthesis of the nicotinamide nucleotide coenzymes (Section 8.3). 

In mice fed a tryptophan-deficient diet ad libitum for 1 week, Jones et al.31 reported on tissue serotonin synthesis rates, systemic tryptophan metabolism, and its response to steroid or cycloheximide treatment. In the experimental mice, brain serotonin synthesis was decreased while duodenal serotonin synthesis was increased following a tryptophan load. Liver total protein was depressed in experimental mice but increased following a tryptophan load. Blood tryptophan (total and free) and albumin were decreased in experimental mice, but ratios of albumin-bound tryptophan were increased. Enzyme kinetic studies indicated that, in experimental mice, brain tryptophan-5-hydroxylase had a reduced Vmax but the enzyme response to tryptophan or hydrocortisone injection was increased. However, hepatic tryptophan-2,3-dioxygenase response to tryptophan or hydrocortisone injection was blunted in experimental mice. 

Total chemical synthesis confirmed the structure of both substances and showed that enteramine and serotonin were completely identical. The true and chemically correct name is 5-hydroxytryptamine (5-HT) and this should be used rather than the old and misleading historical names. 

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