[uglepik]

Hi!

I'm searching for a mild cleavage method, that will leave my sec. boc-groups on the cleaved product. So, I stumbled on this one:  DCM:TFE:AcOH (8:1:1) (TFE:trifluoroethanol). It seems to be quite established as a method for obtaining protected peptides. Most stuff I've read says cleavage should take about 30 minutes to 2 hours.

http://www.2-chlorotritylresins.com/#1

I'm working with compounds attached to the resin through a primary amine and also, the perhaps more conventional, attachment through the carboxylic acid.

AND, my cleavage seems to take a lot longer than the mentioned 2 hours. After two hours, in both cases, it coughs up a yield of 15-35 percent. And even very long cleavage (days) doesn't seem to yield the full expected theoretical crude yield (determined through consistent Fmoc absorption tests). I have checked the poor-yield crude product and it is the right product, meaning that cleavage does take place.

So my question is this:

Does anyone out there have any experience with his cleavage cocktail? On treatment time especially, but also on other conditions. Any advice or discussion would be greatly appreciated.

Regards,
Andreas

[enahs]

How much are you running through your resin and how much product do you have? It almost sounds like you are just using up all your acid.

[uglepik]

How much are you running through your resin and how much product do you have? It almost sounds like you are just using up all your acid.

For each attempted cleavage I've used 0.5 mL AcOH (0.5 mL * 1.049 g/mL : 60.05 g/mol = 8.37 mmol)

The nominal loading capacity of the resin is approx. 0.3 g * 1.3 mmol/g = 0.39 mmol

However, the actual coupling to the resin has been estimated by fmoc absorption test to be: 0.121 mmol

It seems unlikely that I should use up all my acid. Especially since I have repeated this twice. However, it may be that I get below some magical threshold AcOH concentration where cleavage rate drops dramatically. But I also think that sounds unlikely :-)