[Mr Amino]

Hi, I am a biochemist who needs some synthetic OC help.  Basically I want to add a methacryloyl group to L-DOPA (3, 4-dihydroxyphenylalanine).  The problem is that the 3,4 catechol will oxidize in basic solution.  I found a method that uses borate buffer to protect the catechol but I have a few questions if you dont mind lending me your supreme OC skills.  The procedure is below followed by some questions.

1.15 g (5.69 mmol) of Na2B4O7 was dissolved in 30 ml of water.  The solution was degassed with Ar for 30 min, after which 0.592 g (3.0 mmol) of L-DOPA was added and stirred for 15 min.  0.317g (3.0 mmol) of Na2CO3 was then added, the solution was cooled to 0C, and 0.3 ml (3.0 mmol) of methacryloyl chloride was slowly added with stirring.  The pH of the solution was maintained above 9 with Na2CO3 during the reaction. After stirring for 1h at room temperature, the solution was acidified to pH = 2 with concentrated HCl.  The mixture was extracted with ethyl acetate three times.  After washing with 0.1 N HCl and drying over anhydrous MgSO4, the solvent was removed in vacuo to yield crude light brown solid.  The product was further purified by elution from a silica gel column with dichloromethane (DCM) and methanol (95:5).  After evaporating the solvent, a white, sticky solid was obtained with a product yield of 35%.

1.  First thing i notice is that the final work-up doesnt seem optimal.  Is there a better way to do this or do you think most of the brown crud is just oxidized DOPA that cant be removed at this point?

2.  Would using a higher conc. of borate minimize oxidation, increasing yields, and decreasing brown crap or would it hinder the reaction?

3.  Would using a molar excess of methacryloyl chloride increase yields is the small yield dependent on DOPA oxidation?

4.  Is chromatography using 95:5 DCM:methanol the way to go here?

Thanks for any help.

[nocommentes]

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[Mitch]

The work-up seems fine. I would go ahead and attempt it. If there is any serious complications come back.

[Mr Amino]

Thanks, ive just been having a problem with small amounts of impurities forming.  Using TLC, i get a large spot for my main compund and 2 faint, slightly less polar spots.  I think this is the methacryloyl group adding to the OH groups on the catechol.  The only real problem is that this doesnt completely seperate with column chromatography and i lose material.  

This is more of a specialized area so i dont expect anyone to give me a cure-all answer but i just thought id throw it out there.

[Mitch]

Was the TLC's retention time 0.3?