Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b11762
https://ift.tt/2GteHXV
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c10057
Lin Zhang, Eckhard Bill, Peter M. H. Kroneck, and Oliver Einsle
https://ift.tt/34WvvUa
I saw an old thread about SAMe where it was being considered for sale if the downsides could be addressed. Is it still being considered? What things are there to be aware of when supplementing SAMe? It's been reported to have a positive impact on joint pain so I wanted to give it another try.
I had a hard time searching reddit due to the abbreviation and the new reddit search just crapping out all the time so I apologize if there are posts about it I missed.
As you're likely aware, Histamine is metabolized in the body in two ways: through methylation via HNMT or oxidation through DAO (link).
If the body possesses elevated histamine, it seems obvious that either of these systems would be activated to a substantial degree, and for those who have less effective DAO activity (resulting in leaky gut and symptoms post-eating), they would more heavily lean towards methylation as a source of removal.
Sam-E is the methylator in the body that is used as a cosubstrate with HNMT to methylate histamine, deactivating it. However, Sam-E is needed for many processes other than histamine metabolism including neurotransmitter synthesis, melatonin production, dna, protein, and lipid methylation.
With histamine intolerance, I see two things: 1) elevated histamine can use up a large portion of Sam-E, which may needed for other processes, or 2) there may be inadequate Sam-E levels to metabolize histamine. Both situations may occur simultaneously.
Has anyone supplemented with Sam-E and experienced benefits? Alternatively, for those who understand the connection between folates and methylation, have you supplemented with methylfolate and seen any benefits?
Hello fellow organic redditors, I've been struggling with the synthesis of AdoDMNB cofator for a while now (SAH alkylation step), this cofactor is used in DNA alkylation and dealkylation (if you're feeling curious, you can read about Epigenetics, quite an interesting topic). If you have some free time, please read ahead, any ideas are appreciated!
The photo of this post: https://i.imgur.com/9P8vT9T.jpg
So the general idea of the reaction is SN2-type nucleophyllic attack of sulphur atom onto a carbon with a leaving group (the amino acid and the aromatic NH2 are protonated, because the reaction is carried out in acetic and formic (1:1) acid solution, hence the most nucleophyllic atom here is S). I've used a series of alkylating agents to produce this cofactor, yet none of the alkylating reagents seem to do the job (reaching only 15% or less conversion).
To make this post easier to comprehend, different alkylating agents are labeled as DMNB + the leaving group abbreviation (like Br, I, OAc, OTs and ONs). DMNB - 4,5-Dimethoxy-2-nitrobenzyl.
Firstly, I've tried DMNBBr and DMNBI (typically I'm using 6 eq. of alkylating reagents, so you can assume I'm using at least 6 eq. in any reaction) in addition to 6 eq. of silver acetate, which helps to polarize the C-Hal bond, making the carbon more electrophyllic, though the reaction slows down to a point where it doesn't proceed at all. In some literature scientists use silver triflate, still in the methods they list yield to be no more than 15%. All of these alkylating reactions were carried out in a mixture of 1:1 AcOH:Formic acid under argon gas.
Also I've tried the reaction with DMNBOAc, but it showed to be too weak of an electrophile (reaction proceeds, but extremely slow, so It's rendered useless in this reaction).
The next thing I've tried are aromatic sulfonates as leaving groups, including tosylate (DMNBOTs) and nosylate (DMNBONs), which on their own were quite a challenge to isolate. DMNBONs purified by column chromatography showed immediate equilibrium in solution with some 5 to 6 colorful, decaying after exposure to light compounds on TLC. The nosylate showed poor results in just the acid mixture (only trace amounts were detected by HPLC-MS), yet the addition of NH4OAc gave much better results (conversion was about 10-12%), but after some hours the reaction stopped completely. Using DMNBOTs showed similar results, not using NH4OAc the reaction went smoo
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