How many permutations (carbon only, no heteroatoms) of this cocaine derivative do not

[Nagelfar]

...violate any rules?

R1-3: any combination of H (not a het.at., but i.e. no carbon bond) a single methylene unit (planar, beta or alpha) a double bond, or a triple bond (where it doesn't make more than four by being adjacent to a double, of course)

There's no oxygens, but being pure carbon (besides the number of bonds) are there any rules I am breaking with certain combinations (rules like for instance possible with a heteroatom: 'keto–enol tautomerism') of the above?

I ask because of the drastic difference between 224a and 224d with binding; with the incredible selectivity of binding versus uptake of 224c, why weren't extra-carbon bonds tried along it in differing combinations?

I'll show some individual instances besides my R-substitution image above:

^^This one feeling like it is violating something, is it?^^

Anywho, at home I drew like over 60 permutations of the above, and I began to legitimately wonder which were wholly fiction on our environment here on Earth. I was going to make a chart with them all, and number them so someone could just call out the numbers of those which do not work in real world physics, like a strange game of cocaine analog bingo.

I may still do that if this doesn't get my question satisfactorily answered.

 

[aced126]

The one you have your doubts of is not "violating anything" as of such, but remember the structure with that double bond will mean that section of the molecule is completely planar, and that could, and I suspect does, affect greatly the binding affinity.

The triple bond molecules are drawn in a way that are not representative of how they would look like in reality. Substituents on C-C triple bonds are linear, so the phenyl ring would be at 180 degrees relative to the triple bond, and so would the rest of the molecule. The fact that it's fixed to that conformation and can't move makes me think that the triple bond ones won't show good affinity.

 

[Nagelfar]

The one you have your doubts of is not "violating anything" as of such, but remember the structure with that double bond will mean that section of the molecule is completely planar, and that could, and I suspect does, affect greatly the binding affinity.

Got you, yes I knew it couldn't be R or S when doubled in that way, but note that R-allococaine ('allo-' prefix =ing "S" @ C3) is the next most potent isomer (even though even "the next most" is still a drastic reduction potency-wise) but seeing as benztropines work well in the C3 alpha configuration I'd assume a planar (unless for whatever reason it doesn't grip at all due to a 'cupping' shape when either R *or* S) would be roughly half way between the best and 2nd best cocaine isomers; and the C3 is longer than cocaine proper like the GBRs created after benztropines which may play a role in C3s flexibility at binding.

The triple bond molecules are drawn in a way that are not representative of how they would look like in reality. Substituents on C-C triple bonds are linear, so the phenyl ring would be at 180 degrees relative to the triple bond, and so would the rest of the molecule. The fact that it's fixed to that conformation and can't move makes me think that the triple bond ones won't show good affinity.

Now *this* I didn't know (always learning), by 180 degrees, do you mean from at the point of the triple, the remainder out to the phenyl would be, how do I describe what I am envisioning; that wouldn't point *toward me* from the flat surface of the computer screen. (that'd be 90 degrees in 3D); can what you are saying be depicted with just 2D, and if so do you mean this? (using the final, above, triple bond example I gave):

or this?:

I suppose your saying "and so would the rest of the molecule" is what throws me even more. (i.e. if one half of it from one point; to the phenyl, is 180 degrees; and if from that point back to 'the rest of the molecule' were also 180 degrees, wouldn't it still be all in the same direction?)

 

[SquidInSunglasses]

He means the angle between the two adjacent bonds (for example in this case, the Ph-C bond and the C-C triple bond) is a straight line. If you take that carbon atom as the centre of an angle formed by its two bonds, the value of that angle will be 180 degrees. That is what a bond angle of 180 degrees means.

You probably shouldn't be messing around with organic chemistry if you don't understand even something college-level like bond angles. There's plenty of sources out there to learn this sort of thing, and you should really make sure you have a solid baseline of understanding before you start looking into something complex like 3D organic compound structures.

 

[aced126]

https://en.wikipedia.org/wiki/Acetylene

Look at the image Wikipedia provides.

 

[sekio]

Triple bonds are straight lines - they cannot have 90 degree kinks in them.

 

[Nagelfar]

Thanks aced & sek, so basically my question of any limitations meant *this* little facet. It's useful for me to know, since it's still a tenable bond in this case but only at one place since it'd be where the two bonds between the three bonds of a single length can all be straight.

He means the angle between the two adjacent bonds (for example in this case, the Ph-C bond and the C-C triple bond) is a straight line. If you take that carbon atom as the centre of an angle formed by its two bonds, the value of that angle will be 180 degrees. That is what a bond angle of 180 degrees means.

You probably shouldn't be messing around with organic chemistry if you don't understand even something college-level like bond angles. There's plenty of sources out there to learn this sort of thing, and you should really make sure you have a solid baseline of understanding before you start looking into something complex like 3D organic compound structures.

It's not the organic chemistry that had me bemused, it was non-explicit vernacular of the answer. For an example simply saying "look at RTI-298", and I'd have had it. I jumped right into one of the most difficult, chiral, compounds as my first chemistry interest. But the very tradition of chemistry itself did the same thing (cocaine being the very first biomimetic synthesis in history), so my karma yoga is a little bit more "actus purus" than your usual individual pursuing organic chemistry: all my knowledge (since I began paying attention in 2007) has been as a hobbyist, no academic background, and I never bothered with the basics, if I can't learn from the top down, it's not interesting to me. I like starting big.

 

[sekio]

since it's still a tenable bond in this case but only at one place since it'd be where the two bonds between the three bonds of a single length can all be straight.

I can't parse this sentence.

Those structures you drew actually make my head hurt. Your depiction of the triple bond is particularly wrong: there is absolutely no way you can have a bond like that with a 90 degree kink on each end.

If you want to get a better idea of how these molecules look as 3d structures (and have a copy of chemdraw suite), I suggest you draw them in chemdraw as 2d molecules and then import them into chem3d. Then perform a MM2 energy minimization it will move the atoms around until the repulsive forces between them are at a minimum.

most difficult, chiral, compounds

Uh, well, let me introduce you to marine natural products. You think cocaine is bad, try working out the stereochemistry of maitotoxin in your head sometime, eh?

 

[Nagelfar]

I can't parse this sentence.

Those structures you drew actually make my head hurt. Your depiction of the triple bond is particularly wrong: there is absolutely no way you can have a bond like that with a 90 degree kink on each end.

I inquired (the purpose of the thread) because I *didn't* know. But thanks, the sentence you couldn't understand was validating the "particularly wrong" summation of your above insight.

Uh, well, let me introduce you to marine natural products. You think cocaine is bad, try working out the stereochemistry of maitotoxin in your head sometime, eh?

I meant small, drug-like compounds. Of course proteins, polymers etc. discounted. I mean, technically I guess someone could consider an *entire human being* to be one big molecular structure. Try drawing the mean-value of a human in its entirety out as a space-filling or ball & stick 3D molecular structure(!) ;-p

 

[aced126]

^That marine compound would probably classify as a small molecule; it isn't a protein nor a polymer.

You can have angled triple bonds, but they are normally extremely unreactive and definitely cannot be isolated. For example, look at nucleophilic aromatic substitution via the benzyne mechanism.

 

[Nagelfar]

^That marine compound would probably classify as a small molecule; it isn't a protein nor a polymer.

It's an interesting one for its complexity, certainly.

 

[sekio]

And also a total synthesis challenge for people who think the total synthesis of vitamin B12 is too easy...

 

[aced126]

And also a total synthesis challenge for people who think the total synthesis of vitamin B12 is too easy...

What I don't get is how anyone can actually determine the structure of something like that.

 

[Nagelfar]

What I don't get is how anyone can actually determine the structure of something like that.

My guess from the point of metaphysical idealism would be observation causes quantum collapse and its the first thing the scientist who first observes it's subconscious projects into it, which is promptly validated through empirical discovery. (*rhetorically facetious comment*)

 

[clubcard]

Conformational rigidity.