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Its not that the signals ultimately do nothing, just that they never directly effect the output. The part I was having trouble with was being used to populate a look-up table - without this nothing else would work correctly thereafter but all that the logic was doing was manipulating some data and storing it in memory - not effecting an output.
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I agree with Tricky, if you really need a no prune here it means there is something wrong with your design. A register/signal is only optimized away if it never has any chance of affecting any output, ever. If there is any way the contents of that memory affects one output, even a lot of cycles after it was written to, then it won't be optimized away by the synthesizer.
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