Semisynthetic LSD

Alkaloids are one of the most important classes of natural product providing drugs for humans since ancient times. Most alkaloids are well known because of their toxicity or use as psychodelic drugs (e.g. cocaine, morphine or the semisynthetic LSD), but many alkaloids have had a deep impact on the treatment of parasitic infections. The outstanding example is quinine (1) from Cinchona succirubra (Rubiaceae) used for the treatment of malaria for more than three centuries. 

These molecules cause significant changes in the perceptual system, producing sensory illusions and inducing a distortion of reality, the sense of space and time, to the point of hallucination. Natural, synthetic or semisynthetic substances can cause hallucinogenic effects psilocin, psilocybin, mescaline, and LSD. Hallucinogenic effects are also created by phencyclidine and ketamine, but these molecules have a dissociative character. 

OLOLIUQUI Indian tribes in Mexico use the seeds from two climbers Rivea corymbosa (L.) and Ipomoea violacea, family Convolvulaceae. Albert Hofmann, the discoverer of LSD, has also isolated from this drug the hallucinogenic ingredient, lysergic acid amide, with an effective dose of 2-100 mg. The related compound LSD (Isysergic acid diethylamide) is a semisynthetic substance, one part of which, lysergic acid, is the characteristic part of the ergot alkaloids. Dr... 

As might be expected, other semisynthetic ergot derivatives, such as methysergide (Fig. 10-9) and 2-bromo-LSD, act similarly. Other unrelated structures that have antitryptamin-ergic (antiserotoninergic) actions while simultaneously exhibiting other unrelated actions are cyproheptadine and ketanserin. 

A representative of the simple lysergic acid amide derivatives is the semisynthetic diethylamide, LSD (lysergic acid diethylamide), which has a questionable reputation. Although LSD is not really a natural product, the discovery of its powerful hallucinogenic properties by Hofmann in the 1940s led to the development of the broad field of psychopharmacology. 

Alkaloids are always compounds isolated from nature. However, there are many examples of alkaloid derivatives with a high profile which may be confused and sometimes classified as alkaloids. For example, Lyserg Saure Diathylamid (LSD) (LSD-25) is prepared by the amidation of lysergic acid, itself derived from the ergot alkaloids. Methamphetamine is prepared by the reduction of (-)-ephedrine, and heroin is prepared by the acetylation of morphine, and there are many derivatives of alkaloids which are pharmaceutical products. These semisynthetic compounds can be classed as alkaloid derivatives. 

From (4), ergot alkaloids, classified as indole alkaloids are isolated.The noted semisynthetic hallucinogen LSD was prepared from lysergic acid derived fixim these alkaloids. Ibogaine, psilocine, 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine are also hallucinogens which are classified as indole alkaloids. 

HPLC was proven to be the most important instrumental analytical method for determination of EAs. Separation on HPLC and downstream detection by fluorescence detector or tandem mass spectrometer was performed. In the early 1970s, when the semisynthetic lysergic acid diethylamide 28 (LSD) became available in the drug scene, there was the need of a suitable analytical method for the detection of LSD. Since then, many HPLC analyses have been developed for the detection of EAs. Initially, normal phase HPLC was used for the determination of 4 with subsequent fluorescence detection. Today, reversed phase with C18 column materials is used more frequently for analysis of EAs [63, 71-73]. As mentioned before, EAs differ often in the position of the double bond in ring D of the 2. Clavine-type EAs contain sometimes a double bond at C-8 and C-9, whereas 3 and 4 carry a double bond at C-9 and C-10 instead, which influences the chromophoric features and is therefore a key parameter for the choice of excitation and emission wavelength of fluorescence detection. Extract mixtures containing EAs with a double bond at different positions (C-8 and C-9 or C-9 and C-10) should be analyzed in two runs to ensure the detection and quantification of the complete EAs. Another possibility is to use two fluorescence detectors subsequently [74]. 

LSD is used as a drug of abuse and has potential medical applications. There are therefore forensic requirements to measure LSD and its isomer iso-LSD in body fluids including urine. LSD is considered a semisynthetic drug, being made from some naturally occurring ergot alkaloids by hydrolysis to lysergic acid, which is then reacted with diethylamine to produce LSD. 

Semisynthetic drugs LSD in biological fluids Christie et al., 1976 Harzer, 1982 Webb et al., 1996... 

---