Re: Synthesis of Glucose

[Spectre]

Regarding this older thread

Not sure if the original author is still interested or not, but this sorta thing is right up my alley, so I figured I might as well add my two cents.

Obviously, as was already mentioned in the thread, no-one has ever bothered to come up with a total synthesis of glucose as there is just no reason – given that it can be obtained from any number of agricultural sources, its just not practical. The same goes for a number of other sugars – however, there are some simple sugars that aren’t know in nature, or not known to be available in any significant quantity to be worth extracting.

Typically, these rarer sugars are the ones with odd-ball chirality, inversions and mirror images of the more common sugars. While not so useful as they are to living organisms, they are useful in the synthesis of large molecule mimics of biologically active compounds.

Often, these sugars are built up from already chiral molecules – like amino acids, but there are other ways to do it.

You could build a sugar in the same way as plants do – from carbon-dioxide, but you’d have the problem of no control of stereochemistry – that’s what the enzymes are good at, holding the molecules in a particular orientation to get a specific stereochemistry.

Anyhoo – while it is fairly easy to use biologically derived compounds for chiral work, it can be done via inorganic means – A protein is mostly filler; a macro molecular scaffold.

Using a surface bound catalyst is one way to force a specific orientation during your reaction (although, as far as these things go, it’s still fairly indiscriminate)
By attaching one or two bulky phenyl rings to a planar molecule, you would force it to approach a surface bound catalyst from the ‘lower face’ only – while this probably wouldn’t be practical for building sugars, it could be used to build a chiral auxiliary that could go on to guide the synthesis of the sugar.
This is, just the most basic of possible ways to do this – undoubtedly there are others, but they’d probably be the subject of a year or two of research.

And off the topic of sugars and onto the left handedness of biological amino acids – surfaces also offer interesting avenues for control of chirality of these too.

Mica, for example, could theoretically provide a totally inorganic framework for a sterioselective synthesis of an amino acid. Not 100% in favour of a ‘left hand’ arrangement, but certainly with a higher ratio of left to right.
It’s even more interesting when you consider that one of the suggested origins of life is around undersea thermal vents.
Mica, found in clay, would have been the primary surface that pre-biotic molecules would have had to associate.
Coupled with the high concentrations of metal ions you get precipitating out around these deep sea black smokers, metals like iron, magnesium and zinc, metals which are crucial to modern enzymatic processes, it all sounds like a recipe for a genuine primordial soup.
This is precisely what one of the guys in the basement lab here at work was working at a year or so back; I don’t think the results were very exciting though. Oh well, I guess you can’t win them all.

[tharkûn]

Typically, these rarer sugars are the ones with odd-ball chirality, inversions and mirror images of the more common sugars. While not so useful as they are to living organisms, they are useful in the synthesis of large molecule mimics of biologically active compounds.

A good number of those are made by simply reacting glucose and using stereoinversion SN2 followed by functional group transformation.

Using a surface bound catalyst is one way to force a specific orientation during your reaction (although, as far as these things go, it’s still fairly indiscriminate)
By attaching one or two bulky phenyl rings to a planar molecule, you would force it to approach a surface bound catalyst from the ‘lower face’ only – while this probably wouldn’t be practical for building sugars, it could be used to build a chiral auxiliary that could go on to guide the synthesis of the sugar.
This is, just the most basic of possible ways to do this – undoubtedly there are others, but they’d probably be the subject of a year or two of research.

Not really what you are describing is a class of catalysts which make affect tacticity, not chirality. If your catalyst is achiral itself, then the best I've ever seen are ones which give isotactic, syndiotactic, hemitactic, etc. polymers. However such catalysts work equally well with R or S (L or D) substrates.

Mica, for example, could theoretically provide a totally inorganic framework for a sterioselective synthesis of an amino acid. Not 100% in favour of a ‘left hand’ arrangement, but certainly with a higher ratio of left to right.

Do you have a specific source? From what I know of the chemical structure that should not be true.

[Spectre]

A good number of those are made by simply reacting glucose and using stereoinversion SN2 followed by functional group transformation.

For the most part I'd agree, but there are plenty of ways that don't start with glucose ... and some of them are fairly wacky (eg, scheme 5 and 6). I can't say I've ever actually heard of anyone around work using a glucose interconversion.

Not really what you are describing is a class of catalysts which make affect tacticity, not chirality. If your catalyst is achiral itself, then the best I've ever seen are ones which give isotactic, syndiotactic, hemitactic, etc. polymers. However such catalysts work equally well with R or S (L or D) substrates.

Indeed, hence why I said they were fairly indiscriminate. If I really could propose an inorganic catalyst that could on its own be chirally selective, I'd be off making large amounts of money right now...

I'd think that between a racemic mixture, a few bulky side chains and a surface bound catalyst, you'd get the beginnings of chiral separation - even if it is just limited to a few patches on the surface of the substrate.

Do you have a specific source? From what I know of the chemical structure that should not be true.

Not exactly. This was gleaned from a discussion along the lines of 'so what is everyone up to' down at the pub. I've been down to see the guy and he seems to be denying all knowledge - Either he's rather busy or he doesn’t want to be reminded of something that didn't pan out. It may not have been mica, possibly something porous like Zeolite.
In any case, I did manage to dig this up.
Not exactly sterioselective, but it does create localised areas of enatio-purity, on the nano scale at least.

[tharkûn]

For the most part I'd agree, but there are plenty of ways that don't start with glucose ... and some of them are fairly wacky (eg, scheme 5 and 6). I can't say I've ever actually heard of anyone around work using a glucose interconversion.

Do they not teach history anymore? Interconversion tends be an extremely inefficient process and the getting the right hyrdoxyls is bloody annoying, but it was a straight forward shot that doesn't require a good knowledge of transition metal catalysis.

Indeed, hence why I said they were fairly indiscriminate. If I really could propose an inorganic catalyst that could on its own be chirally selective, I'd be off making large amounts of money right now...

That and collecting your nobel

I'd think that between a racemic mixture, a few bulky side chains and a surface bound catalyst, you'd get the beginnings of chiral separation - even if it is just limited to a few patches on the surface of the substrate.

Nope. You have leaving group or substrate steriocontrol with those. You can make pure R or S polymers, but those achiral catalysts can be initiated with either. You need catalytic control to work off the catalyst and that requires a chiral catalyst, polarized light, screwball magnetics, etc.

It may not have been mica, possibly something porous like Zeolite.
In any case, I did manage to dig this up.

Some minerals grow into enantiopure crystals under certain conditions. The problem is for every S you have an R and they are energeticly equivalent.

None of the Mica class I am familiar with do this.

Not exactly sterioselective, but it does create localised areas of enatio-purity, on the nano scale at least.

Not close to being the same. The energy of interaction in a R-R vs R-S molecule is different (think about a substituated cyclopropane ring), the enthalpy R-R is to all measures equivalent to an SS; likewise R-S is energeticly equivalent to S-R. Indeed it would be shocking if homochiral domains were truely energeticly identical to heterochiral domains (the difference is typicly exceedingly small, but non-zero).

Thus far I have read of nothing which gives rise to chirality which is not chiral itself. Everything which shows chiral bias appears to have 'interacted' with chiral biologicials in some non-trivial way during production and/or purification.

Chemistry-wise I still see no possible way of making pure glucose without starting with chiral precursors or chiral catalysts. To the best of my knowledge all present chiral precursors and chiral catalysts got that way due to a biological influence somewhere back in time.

[Spectre]

Do they not teach history anymore?

*Blinks*
History? In chemistry? ... You've lost me.
What I was saying was; currently, where I work, no one seems to bother with it, hence, I know SFA about it.

That and collecting your Nobel

Mmm, yes, there is that. Although the cynic in me wants to say "but that comes under 'making money' ... then again, how far is a million bucks gonna go these days.

Thus far I have read of nothing which gives rise to chirality which is not chiral itself. Everything which shows chiral bias appears to have 'interacted' with chiral biologicials in some non-trivial way during production and/or purification.

I think my major malfunction here is to conceptually lump asymmetric synthesis in with chiral selectivity - I guess I see them as differing points along the same continuum. Certainly, I don't expect you could whack together something that will just snap crackle and pop out with your correctly oriented hexose, but with enough time, I figure you could figure out a way to at least make a library of sugars and purify out your glucose. But yes, rather wasteful.

Considering that most of the reagents we use come in little white bottles delivered by the Sigma-Aldrich fairy (or the Lancaster gnomes...) it can be hard to tell what is wholly synthetic and what has been derived from a biological source.
It may just be that life is the simplest chemical reaction capable of selective steriochemical behavior.

[tharkûn]

History? In chemistry? ... You've lost me.
What I was saying was; currently, where I work, no one seems to bother with it, hence, I know SFA about it.

Long, long ago before chemists understood transition metal catalysis worth a damn you were extremely hard pressed to make sterioselective additions. Way back when using SN2 to invert steriochemistry was far more common. The problem with that is even under optimal conditions you had 3 reactions in series and I'm sure you know what that does to yield.

When you do the type of work you linked, you are using 3rd or higher generation catalysts/reagents. If you far enough back up the chain of what was used to synthesize what, you reach biologicals and a good number of the "unnatural" chiral reagents and substrates were derived from SN2 inversions of biological materials. There are archeobacteria that have been using that trick for millenia.

I think my major malfunction here is to conceptually lump asymmetric synthesis in with chiral selectivity - I guess I see them as differing points along the same continuum.

They are not. Enantiomers are mirror images and to all achiral measurements (i.e. unpolarized light) the free energy of formation is equal. If you start with achiral reagents, catalysts, and environments you will get racemic products which can be trivial or holy terrors to seperate out.

Certainly, I don't expect you could whack together something that will just snap crackle and pop out with your correctly oriented hexose, but with enough time, I figure you could figure out a way to at least make a library of sugars and purify out your glucose.

You could purify out your glucose and its enantiomer. However those two molecules will have almost all molecular properties in common (i.e. mp and bp). The way we currently purify it further is to use another chiral substance, typicly a solvent, where the energy of interaction between the solvent and each enantiomer would be different. Such solvents were at some point in time derived from something which owes it chirality to life.

Considering that most of the reagents we use come in little white bottles delivered by the Sigma-Aldrich fairy (or the Lancaster gnomes...) it can be hard to tell what is wholly synthetic and what has been derived from a biological source.

It gets a bit sketchy. Let's say you do an addition to chloroethene (normally made from oil and HCl, but pretend carbon dioxide and HCL), obviously you will get a chiral substance or a racemic mixture. If you use one of the numerous chiral transition metal catalysts commericially availible you easily make pure R or pure S, but where did the transition metal catalyst get to have uniform chirality? Well back at the factory they either used chiral reagents or chiral catalysts to make your catalyst. We can then examine how each of those were made and normally in two to twelve steps you reach something which "got" its chirality from nature. That reaction may have been 40 years ago, but current chemistry still requires a biological influence somewhere in the chain.

This is why some very bright minds once proposed making uniform chirality the gold standard of detecting alien life; it isn't because some other very bright people point out that we have no way of knowing how many false negatives that would produce.

It may just be that life is the simplest chemical reaction capable of selective steriochemical behavior.

There is a truly massive debate about exactly how life became uniformly chiral. It gets rolled into the whole abiogensis debate about what made life, but it is extremely poorly understood.

Once you get a uniformly chiral susbstance, the ball rolls right along with minimal effort, getting that starting point is the sticky point.

[CyberNeko]

Wow, thanks!

Those are pretty useful information, many thanks!

Amino acid being used to make sugar, interesting idea. It seem to be suggested in my older books on biochemical compounds but never fully explained.

Like I said on my old thread, it's for basically for story I'm writing. How could you have nice, big farms on starships, let alone have the power to keep it going? ( Yes I know it might be more efficient to just farm it out with alage, but I wanted some second opinions. )

Again, thanks for the informations!