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Let's don't forget that Alois Ruf built many air cooled 3.6 and above motors that made over 550 HP. I know because I drove mine to over 36K miles with no problems. I believe the current owner of my former car has well over 60K on it now...no problems.
To answer your question about Ruf, they were air cooled turbo's.
RUF had NA air-cooled engines back in late 70's....stroked from original specs if my memory serves me correctly. Obviously not 500Hp back then and not sure what more recent versions have in HP dept but they have definitely have made non turbo cars
So will you be using titanium internals? How bad will the low end torque suffer? I am amazed that an air cooled engine can do this naturally aspirated. Learning a lot here.
Good news. Latest dyno run of Cartridge 4 liter, 2-valve, normally aspirated, air cooled engine on street gasoline and with a catalytic converter produced 455 HP and 453 Nm of torque.