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| | From:  MikeKL5 (Original Message) | Sent: 3/29/2005 7:01 PM |
Hey Steve and Others, Thanks for your help on the crystallization question. I guess that dealing with substances that are difficult, if not impossible to crystallize is just one of the perks of being a chemist. lol. I've come across another problem in my research, and I wanted your advice. I recently synthesized 1-(3',5'-di-O-acetyl-2'-trifluoromethylsulfonyl-beta-D-ribofuranosyl)-uracil from 1-(3',5'-di-O-acetyl-beta-D-ribofuranosyl)-uracil. This amounts to converting they hydroxyl group on C2' to a triflate group. I know that triflates can be unstable. I've had this stuff for about two weeks now, and I've kept it in a freezer at -15 C, and away from light. However, both TLC and NMR seem to indicate that the compound is decomposing over time. I am going to synthesize a new batch of 1-(3',5'-di-O-acetyl-2'-trifluoromethylsulfonyl-beta-D-ribofuranosyl)-uracil on Friday, and use it for the sole purpose of trying to measure the rate of this decay. My question is, what else can I do to keep this triflate stable? I think that I've done a pretty good job of keeping the triflate safe from heat and light, but it seems to be decomposing anyway. Do you know any tricks that might be helpful in this situiation? Thanks in advance, MikeKL5 |
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| | | From: ·Steve· | Sent: 3/30/2005 6:23 AM |
Hi Mike, all I can think of is residual moisture slowly hydrolyzing your compound. Do you know yet if the degradation product(s) include your starting compound (now with inversion of configuration at C2' )? With no free OH or other nucleophilic groups in the compound itself, one would expect it to be stable. This reminds me of some peptides I once worked with. Even stored at around -50°C as dry solids, racemization occurred very slowly. This occurred more rapidly if the compounds were stored as frozen aqueous solutions, and most rapidly in aqueous solution at room temperature. In your case, besides moisture, any impurities containing a nucleophilic group, such as un-triflated starting compound, or compounds not completely protected at the 3' and 5' positions, would be suspect. But, this may just be one of those durn compounds that you have to use quickly before significant decomposition occurs.  Steve |
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| | | From: MikeKL5 | Sent: 3/31/2005 1:40 PM |
Steve, Unfortunately, I think that you're right regarding this being a compound that will have to be used relatively soon after it is synthesized. The overall goal of my research is to find a way to synthesize 18-FMAU faster than can already by done by the existing automated synthesis. The triflate is supposed to be the immediate precursor to the fluorinated compound. If the triflate isn't stable, then it would have to be made on-site, and I don't know how that will square. *sigh* I still have to try fluorinating the triflate, and see if the steric hinderance can be overcome so that that reaction will happen at all. Thanks for the advice about trace water. I know that there has to have been trace amounts of water in the flask that I was storing the triflate in .I had opened it to the atmosphere several times. I figured that since it was flushed with Ar it wouldn't matter, but I guess that wouldn't keep all the water out. Oh well, I'll make a new batch and see how it goes. We're going to measure the rate of decay with this batch (or try to). I'll keep you posted. I can't thank you enough for all your help Steve! THANKS!!! MikeKL5 |
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| | | From: ·Steve· | Sent: 4/1/2005 10:16 PM |
OK Mike, wish I could have been more helpful! You might try leaving the compound in vacuum overnight or longer (flask attached to a vacuum pump) to remove as much water as possible. I often left moisture-sensitive solids in vacuum permanently (the flask was attached to the vacuum from a lyopholyzer) since it was convenient and the lyopholyzer was on all the time anyway. Who knows, it may help! Good luck with the project, I enjoy hearing from you about how it's going! Steve |
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