Consider the following scenario:
You have an AS2 message in BizTalk Server.
You clear the Request asynchronous MDN check box in the Message Disposition Notification (MDN) settings.
You select the Use agreement settings for validation and MDN instead of message header check box in the Validation settings.
You do not remove the URL in the Receipt-Delivery-Option (URL) option.
In this scenario, BizTalk Server continues to send AS2 messages as asynchronous MDN instead of synchronous MDN.
The fix that resolves this issue is included in the following update for BizTalk Server:
Cumulative Update 5 for BizTalk Server 2016
Microsoft has confirmed that this is a problem in the Microsoft products that are listed in the "Applies to" section.