Cat afraid to play with my other cats

We have five cats in our household: 1 spayed female and four neutered males. The female came to us first. She was a rescue from a storage yard that had a lot of cats. We took her in when she was 3 months. She is about 6 months older than the boys.

When we first introduced her to them, the boys were small kittens, barely older than three months. At first there was a lot of hissing and growling from the female. The boys were too curious about her to be afraid. Pretty soon they were all running around and playing together. In some ways the boys seemed to see her as a surrogate mother. They would follow her around, play with her, come when she called them, and cuddle with her while they slept.

Flash forward seven months and now that is no longer the case. Things have changed dramatically. She tolerates the boys just fine… until they want to play with her. Then everything goes south. She growls at them and attempts to run away. The boys don’t seem to understand that she doesn’t want to play. The more she tries to get away from them the more they follow her. It’s as if they’re obsessed with her. I try to shoo the boys away but that only works for a few moments and then they’re right back to trying to follow her around and play.

When it gets to be too much I separate them by taking her into another room to diffuse the situation. After things calm down, I bring her back out. Sometimes this maintains the peace for awhile and sometimes they immediately start bugging her again. It’s especially bad early in the mornings and after meals.

I play with the boys on a daily basis. Usually, this involves a morning and evening play session. They also get a lot of exercise chasing each other around. I don’t think it’s a lack of play time that makes the boys behave this way.

I’m at my wits end. Our female cat is getting stressed out. There’s been no fights, but if the boys are especially persistent she gets paranoid and goes after them, hissing and swatting. Sometimes this drives them off and sometimes it doesn’t. The boys never hiss at her.

Any advice on what to do?