No doubt the current crop of 450cc four stroke motocross engines are a testament to the kind of power & performance can be achieved from a mid sized single cylinder. However, those engines are not built to withstand sustained operation over time at higher RPM's, which is a primary consideration for a road going bike. They are very "high strung" purpose built motors, where motocross & supercross tracks rarely demand more than 5 to 10 seconds of WOT over the longest straights before a rider is backing off for a tight corner, or when in mid-air over a big jump.
I'd still have thought they could be detuned/refined/developed into 40-50bhp units with the required durability for road use. KTM and Ducati's big twins make well over 100bhp per litre from similar or larger cylinders.