The 71 syntheses of physostigmine yield 33 racemic mixtures and 38 products of a single enantiomer. The first total synthesis of physostigmine was achieved by Julian and Pikl in 1935. The main goal of Julians formal physostigmine synthesis was to prepare the key compound (L)-eseroline (compound 10 in the adjacent diagram), the conversion of which to physostigmine would be straightforward. In one of his earlier works Julian synthesized the ring of physostigmine from 1-methyl-3-formyl-oxindole as starting material, which was discovered by Paul Friedländer. However, the starting material was expensive, and the reduction of a nitrile to an amine (similar to the reaction of compound 6 to give compound 7 in the diagram) with sodium and alcohol did not proceed in good yield. In his second work “Studies in the Indole Series III,” he had improved the yield of amine from nitrile significantly by using palladium and hydrogen. Although he succeeded in the synthesis of the target compound, the route had several drawbacks. First, the chemical resolution of compound 8 is unreliable, and the chemical resolution of rac-eserethole gives optically pure product only after eight recrystallizations of its tartrate salt. Second, the reductive amination going from compound 8 to compound 9 requires a large amount of Na. In the years since this initial work, many other groups have used a variety of approaches to construct the ring system and showcase new synthetic methods.
A physical examination and laboratory investigations may disclose somatic illness complicating the obstetric events, which sometimes provokes psychosis. It is important to obtain the case records of previous episodes of mental illness, and, in patients with multiple episodes, to construct a summary of the whole course of her psychiatric history in relation to her life. In the 10th edition of the International Classification of Diseases, published in 1992, the recommendation is to classify these cases by the form of the illness, without highlighting the postpartum state. There is, however, a category F53.1, entitled severe mental and behavioural disorders associated with the puerperium, which can be used when it is not possible to diagnose some variety of affective disorder or schizophrenia. The American Psychiatric Associations Diagnostic and Statistical Manual, whose 5th edition was published in May 2013, allows the use of a peripartum onset specifier in episodes of mania, hypomania or major depression if the symptoms occur during pregnancy or the first four weeks of the puerperium. The failure to recognize postpartum psychosis, and its complexity, is unhelpful to clinicians, epidemiologists, and other researchers. Onset groups
Postpartum bipolar disease belongs to the bipolar spectrum, whose disorders exist in two contrasting forms – mania and depression. They are highly heritable, and affected individuals (less than 1% of the population ) have a lifelong tendency (diathesis) to develop psychotic episodes in certain circumstances. The triggers include a number of pharmaceutical agents, surgical operations, adrenal corticosteroids, seasonal changes, menstruation and childbearing.