1. For Exchange 2007 Hub servers and later you first need to enable the anti-spam functionality by running cd "c:\Program Files\Microsoft\Exchange Server\Scripts" and  /install-AntispamAgents.ps1 as described here and then go to Edge Transport (or Hub Transport as appropriate) > Anti-spam tab > Recipient Filtering and enable it as described here
  2. For Exchange 2010, instructions are similar to 2007, go to properties >  Blocked recipients and ensure "Block messages set to recipients that do not exist in the directory" is ticked as described  here and here.
  3. For Exchange 2013, see here to enable Exchange anti-spam and then here and here to stop backscatter.  The EMC command is "Set-RecipientFilterConfig -Enabled $trueSet-RecipientFilterConfig -RecipientValidationEnabled:$true