[greenE]

Hi,
I'm trying finding information about nitro group reactivity in nitrofuran, but I have no success.

This is my thing nitrofuran antibiotics are broad specter agents. http://en.wikipedia.org/wiki/Nitrofuran

I would like finding some modification of nitro group that might inactivate activity of these antibiotics.

Idea is that all elements of molecular backbone should be present only that nitro group should be "masked" in some way. Some reversible group should be attached to it.

Can anyone help me, eider by explaining me if it is possible or by pointing me in direction of some publication?
Thank you very much!

[Mitch]

You need to get a book on protecting groups from the library.

[greenE]

I'm more then aware of that.
That was first place where I was looking, but I couldn't find anything.That's the reason for coming here and trying to get some hints from more experienced people.
I'm molecular biologist and I would need that compound for studding bacterial metabolism. Non of people in my surrounding could help me and I was not able finding proper information by myself.

It seams like nitro group is eider not particularly interesting/useful for masking (protecting) or its not so easy to be done at first place.
There are a lot of different nitro-organic reaction but non of those books I consulted is describing anything that might be useful for me. Reversible nitro group reaction (protecting) seams wary tricky!

[orgopete]

What is your question? Are you trying to synthesize one of these drugs, are you trying to understand how they are metabolized, their biological target, etc.?

[greenE]

non.
I'm trying to find some chemists to synthesize those modified drugs for me so that I can study alterations of bacterial metabolism during penetration into eukaryotic cells. (Im also interested in differences between free living and pathogenic bacterial stages) Im interested in biology, this compound is just potential tool I might use.

I already made contact with few labs. But non of them is able modifying nitro group or synthesizing any of nitrofuran drugs in such way that nitro group is protected (giving rise to inactive drug) and that it can be de-protected in vivo what would lead to activation of drug. Reduction of -NO2 into -NH2 cant help me.

some of nitrofuran drugs (all active :-)
http://en.wikipedia.org/wiki/Nitrofuran (same one is given in my first post)
I have access to many bacterial strains. Meaning if anyone can modify any of them there is possibility that I could find suitable bacterial strain for more detail research.

example of modification Im looking for:
exchangeing one of -O atoms in -NO2 for -SCH3 or some other group like ...
I really have no idea how it might be done or if this from line above makes any sense at all. Im floating in almost complete dark when it comes to organic chemistry.

[OC pro]

This is always when biolgists come together with chemists. The biologists have dreams and the chemists task is to put these guys back on earth.
A nitro group can not be modified in various ways. Reduction into nitro is the common way. What can be done is convert it into an amine NH2. This  group can be varied in numerable ways.

[greenE]

Amino group is not suitable for my needs, soo Im looking for other functional groups.

I was told that direct modification of nitro group in those drugs is not directly possible.
But idea that it cant be protected in some of previous steps during synthesis in a way that it can be de-protected and give functional drug is a bit strange.
Reducing it first into amino form and modifying in order of increasing oxidation level of N before proceeding with synthesis dose not sound completely unlogical

I can go with "It cant be done, jet!", "It cant be done by most of chemists" or "It cant be done directly", but "It cant be done." is unacceptable.

[greenE]

P.S. Job and task of chemists is chemistry!

[Biopolmonkey]

If so many people have already told you 'no' ... then maybe it's time to start listening? (For what it's worth, this is not my area of expertise, and I don't know if it is or not).

And yes, whilst chemists are around to do chemistry (and I say this as one who works very much on the line between chemistry and biology), biologists have to remember that just because we can do a lot of really cool stuff, we can't do everything ... and often the thing you want the most, is the thing we are most unable to do.

This is not aimed at you, but generally chemists dislike biologists because they do not seem to have any respect for the subject (I once witnessed a biology lecturer teaching cis and trans using ethene).

[orgopete]

I have access to many bacterial strains. Meaning if anyone can modify any of them there is possibility that I could find suitable bacterial strain for more detail research.

Honestly, I still don't know what it is that is being attempted. Major modifications are readily possible, but I presume that would result in an inactive drug. I am presuming that would not be of interest. Is that correct?

Since you have access to many bacterial strains, what is the problem with using one of the active ingredients?
I did not perform a lit search, but if there are drugs, there will be patents. If it is analogs you are after, the patents should point you in the direction of active compounds.  In those patents will be other analogs. The analogs will have active as well as weakly or totally inactive compounds.

Easier than purchasing or synthesizing analogs is to ask a drug company for access to analogs. Tell them what you are prepared to do. Since you are planning to do it without their financial support anyway, I'll bet they are more than willing to cooperate with you. It can be free research to them.

I suspect someone can be more helpful if you can be more clear in expressing your objectives. Converting a nitro group into a sulfide may or may not be a reasonable chemical conversion. However, the rational for the conversion is absent. I am reading between the lines here. I am not an expert in this pharmaceutical area, but if there is a class of compounds that are referred to as nitrofurans, then the non-nitrofuran analogs will not have the activity of that class.

[OC pro]

And yes, whilst chemists are around to do chemistry (and I say this as one who works very much on the line between chemistry and biology), biologists have to remember that just because we can do a lot of really cool stuff, we can't do everything ... and often the thing you want the most, is the thing we are most unable to do.

This is not aimed at you, but generally chemists dislike biologists because they do not seem to have any respect for the subject (I once witnessed a biology lecturer teaching cis and trans using ethene).

Exactly. We can make a lot of things...but we are not magicians.

[Borek]

but "It cant be done." is unacceptable.

Sure.

Linear water molecules? "It cant be done." is unacceptable.

Metallic sodium that doesn't react with water at STP? "It cant be done." is unacceptable.

Stoichiometric mixture of oxygen and hydrogen (undiluted with inert gases) that doesn't explode when ignited at STP? "It cant be done." is unacceptable.

Concentrated hydrochloric acid that doesn't react with sodium bicarbonate? "It cant be done." is unacceptable.

Sulfuri acid that doesn't dissociated when dissolved in water? "It cant be done." is unacceptable.

Biologist accepting chemists opinion when they tell him something is impossible? "It cant be done." is unacceptable.

 

[sjb]

Just out of interest, what would people use as nitro isoteres anyway? Carboxylates? Amidines?

[OC pro]

Mimicing nitro groups is very challenging due to electronic reasons. CF3 is alike, can also not be degraded from organisms and bacteria.

[greenE]

Major modifications are readily possible, but I presume that would result in an inactive drug. I am presuming that would not be of interest. Is that correct?

I’m actually looking for inactive drug. What we are aiming for is inactivation by modification of nitro group of nitrofuran part of molecules.
Those modifications are actually what Im looking for.

Since you have access to many bacterial strains, what is the problem with using one of the active ingredients?

problem is that those drugs are active and resistant strains that we have are mutants in ways that are not useful for this study.
This is a problem for finding suck variation. I was looking into patent application and analogs, but thing is that there it is not so likely finding some patent for inactive compounds. Simply people don’t want to pay for thing without possibility to earn some money back.

Biopolmonkey and OC pro I don’t want to disrespect in any way.

I’m aware that I’m pushing over the edge here.  Reason for coming here to this forum is because more than evidentially such synthetic procedure is not commonly available in textbooks. I'm scientist and part of my job is pushing limitations. My idea was seeing if someone can push it a bit more when it comes to nitrofuran chemistry and alternatives.

Linear water molecules? "It cant be done." is unacceptable.

Borek I don’t see how is sarcasm constructive approach especially when it is completely wrong.

I still claim that it is unacceptable for the reason that I sow some of interesting structures for which I believe that are possible to be synthesized.
What is going on here is the most likely problem in communication.
I know that some of things are confusing (e.g .Why any one needs inactive drug?…) I cant give you all details of project even if I know that it would help. That’s my big problem :-(
Thank you all for participating in this discussion!

P.S.I was hoping for some sulfur nitride form … Some people suggested and are saying that azido and niitroso instead of nitro group might function. Ive been looking into those alternatives and Im not convinced but it might be…