Magic methyl, also known as 3,4-methylenedioxy-methamphetamine or MDMA, is a psychoactive drug that is often used recreationally for its stimulant and hallucinogenic effects. It is classified as a Schedule I controlled substance in the United States, meaning that it has a high potential for abuse and no accepted medical use.
MDMA was first synthesized in 1912 by a German pharmaceutical company, but it did not become widely known until the 1970s, when it began to be used recreationally as a "club drug" in the United States. It is typically taken in the form of a pill or capsule, although it can also be snorted or smoked.
The effects of MDMA can vary widely depending on the individual and the dose taken. It can produce feelings of euphoria, increased energy, and altered sensory perception, as well as a sense of emotional openness and empathy. These effects are often described as "magical" or "mystical," which has contributed to the drug's popularity and its nickname of "magic methyl."
However, MDMA can also have negative side effects, including increased heart rate and blood pressure, dehydration, and anxiety. In high doses, it can lead to severe health problems, including overheating and organ failure, and can be fatal. There is also a risk of developing psychological problems, such as depression and anxiety, after taking MDMA.
Despite its potential negative effects, MDMA has also been studied for its potential therapeutic uses. Some research suggests that it may be helpful in treating post-traumatic stress disorder (PTSD) and other mental health conditions, although more research is needed to confirm these findings and to determine the long-term safety and effectiveness of the drug.
Overall, it is important to understand the risks associated with taking MDMA and to be aware of the potential negative consequences of using the drug recreationally. While it may produce short-term effects that are perceived as pleasurable or "magical," the risks of using MDMA far outweigh any potential benefits.
The second half of the book details the many rewards of healthy methylation such as the prevention of heart disease, strokes, arthritis, depression, osteoporosis, and dozens of other diseases -- even chronic fatigue syndrome. NOTES: 1 In the "you just never know what's gonna happen when you wake up on a given day" department, Some nutlog recently read the dimethylmercury article and was arrested by the FBI for 2 Both of these chemicals have caused laboratory accidents which resulted in death. Scheme 68 Polarity-match-based approach for selective C sp 3 —H alkylation; a yield calculated from a calibrated GC assay. The selective activation and functionalisation of C sp 3 —H bonds saw further development when Chen described the use of a PA directing group in the C—H methylation of a diverse family of amine derivatives 169 The methylation protocol displayed good to excellent selectivity for the functionalisation of unactivated C sp 3 —H bonds γ to the directing group. The upshot, White says, is that this reagent will now make it simple and cheap for drug hunters to insert "magic methyl" groups into their molecules. A Use of MnF 3 as an alternative oxidant.
Zinc bis phenylsulfonylmethanesulfinate , a free-flowing, bench-stable solid, was developed and employed in the presence of 5 equivalents of TBHP to install the phenylsulfonylmethyl group on a diverse range of heterocyclic scaffolds. Boyd: Alistair graduated with an MChem from the University of York and completed a research project on the use of vibrational spectroscopy to quantify impurities in pharmaceutical intermediates. In 2013, Shi 170 and Chen 167 contemporaneously reported the C sp 3 —H methylation of amino acid derivatives appended with the 8-AQ directing group, using methyl iodide as the methyl source via a CMD mechanism. Finally, despite the pioneering reports discussed above, the enantioselective C—H methylation of both C sp 2 —H and C sp 3 —H bonds remains conspicuously underdeveloped. Subsequent C—H cobaltation followed by transmetalation with Me 3B 3O 3 introduced the methyl group to the metal centre. Science and AAAS are working tirelessly to provide credible, evidence-based information on the latest scientific research and policy, with extensive free coverage of the pandemic. Some machine help in all this would be welcome, but I'm not sure when we'll see that arrive.
Newly discovered ‘magic methyl' reaction could turbocharge the potency of some drugs
When you add in cell membrane permeability, pharmacokinetics, metabolic stability, and all the rest of it, well, things can get pretty wooly. Scheme 69 A α-C—H methylation of THPPs and related systems. Acknowledgements The authors are supported by the Centre for Doctoral Training in Synthesis for Biology and Medicine, generously supported by GlaxoSmithKline, MSD, Syngenta and Vertex. This could help "across the board" in drug discovery, says David Rees, chief scientific officer of Astex Pharmaceuticals. In particular, the electrophilic nature of the phenylsulfonyl-methyl radical enable efficient reaction with electron-rich heteroarenes. Scheme 22 Co-Catalysed C—H methylation utilising a broad range of DGs and applied to the late-stage functionalisation of select drug compounds. The α-C—H methylation of primary unprotected amines, however, presents unique challenges, requiring an alternative approach.
Methyl Magic: Maximum Health Through Methylation by Craig Cooney
Scheme 41 Activation of MeOH under high energy irradiation and subsequent visible light photocatalytic modification. Contributions are fully tax-deductible. Mechanistic studies supported the possibility of a radical process, and the rate-determining step appeared to be highly dependent on the electronics of the substrate. The methylation protocol was successfully applied to an L-phenylalanine substrate, with no observed racemisation of the amino acid stereogenic centre. In 2020, Seebeck managed to assemble a synthetic replica of nature's methylation framework, allowing for the synthesis of β-methyl-α-amino acids, a prevalent motif in natural products 194 Functioning through a combination of bacterially grown enzymes and co-substrates to facilitate artificial metabolism, numerous L and D β-methylated amino acids were produced on small scale with high diastereoselectivity. Yu, Science, 2016, 351, 252 b Q.
New chemistry makes ‘magic’ drug improvements easier
Diverse downstream reactivity was achieved from the newly installed methyl group, with C—H alkylation and two-step oxidation-amination being exemplified amongst other transformations. While this chemistry enabled the generation of methyl radicals under mild conditions, an alternative approach focuses on the facile, thermolytic cleavage of organic peroxides. Applicability to late-stage methylation was also demonstrated, resulting in the synthesis of methylated fenofibrate and ezetimibe analogues. I'm sure that if you start yanking those nitrogen atoms out of the structure above in favor of good ol' carbons that it'll start losing activity with great speed and thoroughness, for example. Carbopalladation and subsequent β—hydride elimination then furnished the methylated- E-olefins with high geometric selectivity. The related auxiliary triazolyl TA was also successfully applied in the ortho C—H methylation of anilides.
Methyl groups are very common in drug molecules. A potential solution to this lies in the development of bespoke methylating reagents which show more optimal reactivity profiles. Tandem C—H activation sequences offered the opportunity for the rapid generation of value-added substrates, as showcased by the two-step amination and methylation of quinoline- N-oxide alongside the dialkylation of simple pyrazines. Leitch: Jamie obtained his MChem at the University of Bath in 2014 then pursued a PhD at the same institution in the group of Prof. This work not only offered a novel TDG, but also expanded the scope of catalytic C—H methylations of aldehydes. To this end, there remains hope that the recent growth in methodology for C—H methylation will in turn foster new approaches towards enantioselective variants.
Where adding a methyl group does increase a drug's potency, doctors may be able to give their patients less of a drug. In 2017, Ackermann developed a TAM-directed MnCl 2-catalysed C—H methylation procedure with MeMgBr 88 Unlike the previously-reported triazole-directed Fe-catalysed approach, 78—80 the transition to a Mn-catalysed system obviated the need for a phosphine ligand or a zinc additive. Subsequent retro-carbopalladation and norbornene disassociation affords intermediate IV. C—H, 50° , which was hypothesised to cause the substantial binding and potency uplift observed. In 2019, Yoshikai further expanded the repertoire of Fe-catalysed ortho C—H methylations 84 Pivalophenone N—H imines were used as monodentate directing groups given their downstream value as intermediates towards ketones and nitriles.
The prominent role of nitrogen-based directing groups in the site-selective C—H activation of sp 2 centres has been mirrored in their application in C sp 3 —H methylation see Section 2. Many of the reports that followed this work adopted the MeBF 3K methylating reagent discussed previously. Accordingly, several groups have reported conditions to convert THIQs and related structures to the corresponding iminium ions through oxidative methods. He specialised in the remote C—H functionalisation of arenes using ruthenium II catalysis, and completed his training in 2017. Employing a simple carbonyl group as the DG complemented the amidic DGs discussed previously, and allowed for the C—H methylation of readily available aromatic ketones, carboxylic acids, esters and amides. The approach was extended to other alkyl groups in an Ir-catalysed ortho-alkylation of heteroaromatic aldehydes, but in this instance, C—H methylation was only demonstrated in low yield.