Error on Orgsyn, what's next?

I always assumed you can trust Organic synthesis implicitly but now this. Looking for a standard procedure for methylation with dimethyl sulfate I looked at OrgSyn.
Stating they are using the monohydrate but all the calculations were for the anhydrous substrate *shocking* just 124 g/mol instead of 142 g/mol but anyway my trust is gone.....

Another detail in Cannabinoid receptor signaling

Molecular Pharmacology
Fulltext

CB1 Cannabinoid Receptor Activity Is Modulated by the Cannabinoid Receptor Interacting Protein CRIP 1a

Fun with 1-methyl cyclohexenes and cyclic terpnes

Tertiary allylic alcohols are easily rearranged and oxidised to alpha,beta-unsaturated ketones



1. Dauben, W.G. and D.M. Michno, Direct oxidation of tertiary allylic alcohols
A simple and effective method for alkylative carbonyl transposition. Journal of Organic Chemistry, 1977. 42(4): p. 682-685.



Selective ring opening of carene epoxides




Deagostino, et al., J. Chem. Soc., Perkin Trans. 1, 2001, 2856–2860

Review about differences in activation of G-protein coupled receptors

In "fast forward" publication in the Journal of Pharmacology and Experimental Therapeutics Urban et. al review the different effects of agonist and antagonists on GPCRs which are different from the current view of receptor activation. There are more groups of ligands (antagonists, agonists, inverse agonist and partial agonists) but they differ in their activation of second messenger systems.


Highly recommended:
http://dx.doi.org/10.1124/jpet.106.104463

Collection of scanned articles

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Semisynthesis of Salvinicins A & B

Harding et al. synthesised Salvinicins A & B from Salvinorin in two steps. Although the total synthesis of Salvinorin is still not published this work is very interesting as Salvinorin is a kappa opioid receptor agonist while the authors found that another compound derived from salvinorin in few steps is a delta opioid receptor antagonist.

Original article:
J. Nat. Prod.; 2006; 69(1) pp 107 - 112
http://dx.doi.org/10.1021/np050398i

A group of scientist from Hungary and Austria investigated the binding of MDMA synthesis byproducts to the pharmaclogical target of MDMA, the human serotonin transporter. Two compounds inhibited the release of serotonin which is the primary effect of MDMA. These compounds 1,3-bis(3,4-methylenedioxyphenyl)-2-propanamine and N-formyl-1,3-bis (3,4-methylenedioxyphenyl)-prop-2-yl-amine are synthesis byproducts when MDMA resp. MDA is synthesized from piperonal. All other tested byproducts had no relevant affinity to the monoamine transporter. According to the data from the article it is not very likely that synthesis byproducts are responsible for the toxicity of ecstasy.

Original article: http://dx.doi.org/10.1124/jpet.105.084426.

Paroxetine increases blood levels of MDMA

In Clin. Pharmacokinet., 2005, 44(6), 649-660 de la Torre et al gave the antidepressive drug paroxetine (Paxil and other trade names) prior to MDMA consumption. Paroxetine inhibits the CYP2D6 enzyme which is responsible for MDMA metabolism. The authors conclude that CYP2D6 is responsible for less than 30% of the MDMA metabolism.
The combination of paroxetine and MDMA increased the total blood level (AUC) of MDMA and increased the maximum concentration (cmax) while decreasing the amount of the primary metabolite HMMA. The time until the maximum concentration (tmax) is not changed. The elimination of MDMA (ke) is decreased compared to MDMA and placebo.
The authors conclude that CYP2D6 polymorphism is less likely to be linked to MDMA toxicity as MDMA is still metabolised to HMMA by other, unknown enzymes.

Some comments on metabolism and pharmacokinetics of MDMA (Ecstasy)

A research group from Spain investigated the influence of a polymorphism of a liver enzyme (CYP2D6) on the pharmacokinetics of MDMA. Approximately 10% of the european caucasian population are so called 'poor metabolisers' which means that their CYP2D6 enzyme is working slower. MDMA is metabolised by the CYP2D6 enzyme. As MDMA toxicity is related to MDMA blood levels it may be that a part of the population is especially sensitive to MDMA. The metabolism of the CYP2D6 poor metaboliser was slower, resulting in higher MDMA concentrations in blood.

Original article: http://dx.doi.org/10.1007/s00228-005-0965-y