Do you mean that you want to perform a direct reaction with a formation of hydroxylamine derivative R-NH-OR' ? There are some specific reactions; however I think that your real goal is just a conjugation of two molecules. In this case, you have a broad choice of methods based on a functionalization of amine or OH followed by conjugation. For example, you can acylate amine (or OH) with succinic anhydride, e.g. in pyridine or even (for amines) in water. And then react your succinate with nucleophilic component (ROH or RNH2) in the presence of a suitable coupling reagent. It is very simple. If you prepare O-succinate, i.e. RO-COCH2CH2COOH, it can react with amine with amide bond formation in the presence of carbodiimide or other reagent. Or use Mitsunobu or Steglich reaction. There are many variants of this type of coupling.

In Maillard reaction OH groups from sugars react with amino groups (in higher temperature).

I would not choose any high temperature method on more complex molecules. If the hydroxyl group is the one at the anomeric C-Atom of your sugar, it might actually be that you can form the aminoglycosidic bond by reacting both compounds in acidic enviroment. If your hydroxygroup is not the anomeric one, you can maybe use the mitsonobu reaction to form your product. Maybe you can first make the Tosylamine out of the amine moeity and that use this tosylaine as the acid component in a mitsonobu reaction with the alcohol. The attached paper might be helpful. But consider that the stereochemestry of the alkoholmoiety will be inverterd doing this.

Do you mean that you want to perform a direct reaction with a formation of hydroxylamine derivative R-NH-OR' ? There are some specific reactions; however I think that your real goal is just a conjugation of two molecules. In this case, you have a broad choice of methods based on a functionalization of amine or OH followed by conjugation. For example, you can acylate amine (or OH) with succinic anhydride, e.g. in pyridine or even (for amines) in water. And then react your succinate with nucleophilic component (ROH or RNH2) in the presence of a suitable coupling reagent. It is very simple. If you prepare O-succinate, i.e. RO-COCH2CH2COOH, it can react with amine with amide bond formation in the presence of carbodiimide or other reagent. Or use Mitsunobu or Steglich reaction. There are many variants of this type of coupling.

Dear Hossein Shaki

-OH group from sugar will react with -NH2 in higher temperature but it's not recommended and no use for your requirement.

So that you follow -OH and -NH2 activation and enhance coupling methods by using DIC/DIPEA coupling and activation methods,

For this coupling just you give some 30-450C maximum temperature.

You prepare O-Succinate means it will react with amine in presence of DIC/DIPEA just like peptide amide bond coupling

Hope You Clear..,

Good Luck and Regards

R.Selva.....

You follow peptide amino acid coupling method and increase little temperature as selva chemist suggested...

You can also oxidize saccharide ring with periodate, it opens the ring forming two aldehyde groups (You need two –OH at neighboring carbons) , reaction runs in water at room temperature. Then aldehyde groups will react with amine forming imine, also water solution, room temperature… You can reduce it to secondary amine with sodium borohydrate. For saccharides it is a very easy way, and very efficient, check my publication on sealing of dacron vascular prosthesis with dextrane – albumin polymer.

One of the best options is using carbonyldiimidazole (CDI), you can couple the OH with the CDI in organic solvent and then the amine. Anyway you should have a look to "Bioconjugate Techniques" by Greg Hermannson, it is the best text by far regarding this type of questions.

If you have a chiral center and you want not to change it to racemic. So, use methanesulfonate or toluene sulfonate esters, replace by bromine under SN2 mechanism (It will invert the configuration), then make a reaction of the bromo-derivative with N-hydroxysuccinimide, also under SN2 replacement condition. The configuration of the resulted product will be the same of your hydroxyl derivative. Good luck

The simplest option is probaby to form a carbamate.  Phosgene, or an equivalent such as triphosgene, can convert ROH to RO(CO)Cl, which will react readily with amino groups.

Dear Tomasz Ciach

Thank you for your information. My colleague in our laboratory worked on oxidation of dextran with periodate by the method which you mentioned above. But there is a little difference between my polymer with dextran. I used hydrophobic, this new molecule producing micelle structure in aqueous medium. I would like to ask you can I used periodate to oxidize glucose ring in hydrophobic dextran?

Another question: is there any changes in solution's color when you oxidezed dextran with periodate?

Dear Herranz

Thank you for your answer. I "Bioconjugate Techniques"  about conjugation of -OH group to -NH2 group by CDI, something is written about  pH of solution. I would like to know is concept of pH used in organic solvent?

If the final aim is to link the polysaccharide with another molecule without necessarily having (N-O) link, then I suggest the following easy procedure:

1) Oxidize the relevant groups in the polysaccharide using PCC:

RCH2OH → RCHO

2) Condense the aldehyde (or ketone) with the amine:

R'NH2 + RCHO → R’N=CHR + H2O

3) Reduce the resulting imine (reductive amination):

R'N=CHR → R'NHCH2R

Both the groups OH & NH2 are nucleophiles  therefore direct reaction is not possible to form N-O  bond.

yes, you should use CDI. its a common chemistry in the bio material. check below:

I suggest to use this ebook : Bioconjugate

Techniques .. 2nd Edition

Greg T. Hermanson

Pierce Biotechnology,

Thermo Fisher Scientifi c,

Rockford, Illinois, USA

If your synthesis can be modified a bit, and if you were limited to chemical methods only, you could try hydroxylating the amine first (Advanced Synthesis & Catalysis, 2005, 347(9), 1223-1225; J. Org. Chem. 1986, 51(17), 3355-7), and afterwards attaching the sugar component.

Hi, yes the pH is important for coupling in aqueous environment, for NH2 typically 8-10. If you can do at least the OH activation with CDI in an organic solvent it would be much better. Otherwise the breakdown of CDI in water is too large for the reaction to work. You can also use mixtures of DMSO-water and similar

I agree with Nizar. you can also oxidise quantitatively with periodate and then do a reductive amination. Regards. Deon

i have partially oxidized OH groups of polymer with periodate and carried out amination. of PEGamine

Here You have description in our paper, applied in nanoparticles formation:

https://www.researchgate.net/publication/289991753_Dextran_Nanoparticle_Synthesis_and_Properties

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett's esophageal adenocarcinoma, International Journal of Nanomedicine 10(default):6811-6823 · October 2015

Article Dextran Nanoparticle Synthesis and Properties

Not knowing exactly what you are doing, one other way would be to use a di-isocyanate to couple the amine and the hydroxyl group. You can first react the amine with the isocyanate in any aprotic solvent. Use a molar ratio of NH2/NCO ~ 0.5 to react only one of the NCOs. Use a solvent such as acetone or n-pyrrol at less than 60oC. The reaction of amines with isocyanate is fast and easy. Use the isocyanate-amine adduct for attachment to the polysaccharide. This will have to be conducted in anhydrous conditions which is always a challenge in polysaccharides since residual water may react with NCO. There is plenty of di-isocyanates as free samples from suppliers or from catalogs such as Aldrich.

Hydroxyl group and amino group are the both nuclephilic. So no reaction will take place. But when polysaccharide presente on its backbone an anomeric carbone (asymetric carbone) , the situation is completly different. We have here an aldehyde which can easily react with amine to give an imine.

See also reducing sugar (equilibrium between the closed form of the cycle and the opened corresponding form). Best regards.

You can react the hydroxyl compound with a linking agent( i.e: epichlorohydrin, cyanuric chloride) and treat the product with the amino fictionalized compound.

Marius, Read Igor Dubey's answer, above.