The total synthesis of reserpine

Reserpine: A Challenge for Total Synthesis of Natural Products

Use of rauwolfia serpentina benth. in neuropsychiatric conditions

The idea that serotonin plays a role in the maintenance of normal mental functions arose from studies of antimetabolites of this hormone. I t was put forward originally by Woolley and Shaw in 1954* and has seemed to be so useful that it may be advisable now to recall the evidence that suggested it, and some of the subsequent findings that seem further to support it. In living creatures there are a variety of important chemical compounds that are essential for normal physiological functioning. These compounds include such substances as hormones, vitamins, and amino acids. Serotonin is one of these hormones that has a role to play in living processes. One can picture it as causing its effects by combination with specific receptor sites, designed especially to react with it and not with other hormones. The serotonin fits Ihe receptor much as a key fits a lock, and many features of the hormonal structure are required so that the serotonin key will function in the receptor lock. If one now makes a substance that resembles serotonin in several ways, but differs in a few, one may have formed an antimetabolite of this hormone. The analog fits the receptors well enough to combine with them, much as an ill-fitting key can be thrust into a lock, but just as such a related key may not turn the lock, so also one pictures the substance resembling serotonin as being unable to fulfill the physiological role of serotonin. Furthermore, the presence of this substitute prevents the hormone itself from combining with the receptors, and thus brings about a specific deficiency. We have used this crude mechanical analogy so that we may visualize the mode of action of these substances. The antimetabolites of serotonin are chemical compounds that resemble this hormone in structure. They bring about a deficiency of this hormone specifically because they combine with the serotonin receptors by virtue of their structural resemblance to it. The first pharmacological property of serotonin to be discovered was that it caused smooth muscles to contract. Thus it can be used to cause the muscles of the walls of blood vessels to contract, and possibly for this reason serotonin raises blood pressure in an animal. The uterus and the intestines likeLet us first consider what an antimetabolite is.

Evidence for the participation of serotonin in mental processes

Cyclic imine nitro-Mannich/lactamization cascades: a direct stereoselective synthesis of multicyclic piperidinone derivatives.

Reserpine, C33H40O9N2, has been isolated from Rauwolfia serpentina Benth. Reserpine is an ester alkaloid yielding reserpic acid, 3,4,5-trimethoxybenzoic acid and methanol on hydrolysis. Degradation products of reserpic acid make it likely that reserpic acid is a yohimbane derivate, and a hypothetical structure for reserpine has been put forward which is in agreement with the facts known so far.

Die Konstitution des Reserpins. 8. Mitteilung über Rauwolfia-Alkaloide

Chemistry of rauwolfia alkaloids, including reserpine

AusRauwolfia canescens wurde Deserpidin, C32H38O8N2, isoliert und eine Konstitutionsformel fur dieses neue Alkaloid vorgeschlagen.

Rauwolfia alkaloids. XVI. Deserpidine, a new alkaloid from Rauwolfia canescens.

Bei der Permanganatoxydation und der Kalischmelze der Reserpinsaure wurden 4-Methoxy-oxalylanthranilsaure und 5-Oxyisophtalsaure isoliert. Als Arbeitshypothese wird deshalb fur Reserpinsaure eine Yohimbanstruktur postuliert. Durch die obigen Abbauergebnisse ist die Stellung der einen Methoxylgruppe festgelegt, wogegen die Haftstellen der drei weiteren funktionellen Gruppen noch nicht gesichert sind.

On the constitution of reserpine from Rauwolfia serpentina Benth.

Ausgewahltecis- undtrans-Isomere, Derivate des 1,2,3,4-Tetrahydro-1,2-diphenylnaphthalins, wurden beschrieben. Der basische Ather VII blokkierte die Nidation in der Ratte bei einer taglichen Dosis von 20γ/kg per os.

L. Dorfman

Papers

Die Konstitution des Reserpins. 8. Mitteilung über Rauwolfia-Alkaloide

Chemistry of rauwolfia alkaloids, including reserpine

Rauwolfia alkaloids. XVI. Deserpidine, a new alkaloid from Rauwolfia canescens.

On the constitution of reserpine from Rauwolfia serpentina Benth.

Synthetic estrogens and implantation inhibitors.