I've had luck multiple times getting agents to honor a ZED in reverse or for a different city in the same (or lower) fare zone, but I've not happened upon an instance trying to use one issued for a direct flight for an alternate itinerary that includes a layover. It's a pain to tie up $$ with ZEDs, but I would be inclined to at least get one ZED itinerary that included a layover (say a LAX/ATL ZED plus ATL/AMS) and then if that wasn't the most open connecting city, you could try and get the agent to honor it for a different one.

The one potential issue I see there is (using my sample ZED itinerary) say you bought LAX-ATL-AMS but now SFO looks a lot better load wise. While the LAX/ATL leg would definitely be less than a LAX/SFO and should therefore work no problem, you might hit a snag with getting ATL/AMS to count for SFO/AMS. The solution might be to buy the most pricey of each leg--LAX to connecting city, then connecting city to AMS--to have on hand. I don't think I've ever tried to get the difference back when the fare zone for the flight I took was less than the fare zone of the ZED I paid for, so I'm not sure whether you can do that or if you'll just have to be willing to take somewhat of a loss. (Mine was always a nominal amount and I didn't feel like trying to hassle with it.)