I'm not going to post often here since it doesn't happen every day that I synthesize an opioid, much less a novel opioid that I designed myself, but when I do I'm going to post detailed information on the reaction mechanisms and the chemistry of both my own novel opioid(s) as well as novel synthesis routes of known opioids.
One last thing before I go into how to navigate this blog and what to expect: the target audience of this blog is primarily advanced organic chemists, hence why terminology won't be explained. Mere dabblers or non-chem junkies with an opportunistic desire to synth their own supply are at the WRONG place here! Those knowledgeable enough will get enough information to connect the dots and conduct the syntheses for themselves. This doesn't mean however that I won't explain things, even to novices if I get the impression that they are very serious and honest about learning.
The posts in this blog are subdivided in labels of "Compounds", "Novel Compounds", "Novel Routes", "Salts", "PDF" (patent files or interesting research papers) and finally "Test Reports" which you can filter by scrolling to the bottom of any blog post and clicking on the aforementioned categories. All syntheses of both known as well as novel opioids will be posted in the first two sections respectively. Please note that "Novel Compounds" does NOT refer to new opioids on the market, but to my own inventions. Same is true for "Novel Routes". This includes improved syntheses of existing routes. Novel agonists that I have developed myself have to be tested first regarding their toxicity and analgetic potency on wistar rats (particularly valuable due to their high level of genetic homogeneity, ease of handling, and reproducible results). These posts can be found in the "Test Reports" category. The "Salts" label will contain my experiments in solubility enhancement with chemical, physicochemical, and biological considerations. I will be converting base opioids into various salts, from relatively known ones such as hydrochloride and tartrate to the more exotic ones that have never been tried such as punicate (from punicic acid, which is contained in the lovely pomegranate) or cinnamate (mmmh, cinnamic acid). The goal is to find a salt that will make the compound hypersoluble in water while hopefully also increasing the onset and duration of action. To give an example, it was observed that single salt amphetamine in dextroamphetamine preparations was not a good choice for fast and sustainable psychostimulant effects. Instead, Adderall XR® was designed as a combination of the aspartate and sulfate salts of amphetamine, plus the saccharate and sulfate salts of dextroamphetamine. These different salts in a single drug product allowed different metabolism rates and possessed different onsets of action. This resulted in a faster induction of therapeutic effects while maintaining those effects for a sufficiently long time (see https://pubmed.ncbi.nlm.nih.gov/28763533/). Many chemists often underestimate how the physicochemical and biological properties of APIs are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. This means the appropriate salt can improve the overall therapeutic and pharmaceutical effects of a compound, or have a detrimental effect if a bad salt formulation is chosen as shown by the example above.
The opioids that I am interested in and therefore will be posting about, belong to the following families: 4,5-epoxymorphinans, morphinans, 4-phenylpiperidines and related azacycloalkanes (with special respect to a Tilidine derivative of my own that I will be experimenting on myself in the future after having gone through my rat testing protocol), 3,3-diphenylpropylamines, atypical opioids, and lastly I will be experimenting with the N,N-diallyl- and N-methyl-N-allyl quaternary salts of (4,5-epoxy)morphinans since there is some information suggesting how these functional groups make the opioid antagonistic only towards the peripheral effects while leaving the CNS activity untouched (therefore eliminating or at least vastly reducing the possibility of lethal ODs and other non-lethal but obnoxious side effects associated with opioid use such as constipation).
I will be staying faaar away from benzomorphans since most of them don't have any significant MOR agonism (and those that do have it are usually disgusting dualists that feel as crappy as buprenorphine does) and induce more often than not psychotic freakshows which I am not interested in (they are most certainly fascinating from a Quant/Qual SAR perspective, but I will be only documenting those opioids here that belong to the above mentioned families that I am recreationally interested in).
I think that's about it for now. I hope you enjoy your stay here...
