250 HP Slant Six - No Turbo

My .02

slantsix.org....can be a bit rough, but there is some knowlege over there. Try talking directly to DOC, Doug Dutra, Aggressive Ted, etc. If you want to avoid someone in particular ( I understand ), go ahead. I would still hang around and read up a bit, there quite a few there, that have knowledge on your general build....

With that being said, it is going to take a solid build to get to your goals.
The head will be the key. Portwork, oversize valves, etc are going to be critical. Reference HOT ROD's (or was it Car Craft?)build, I think they were close to your goal.
One area that has evolved since their builds is coatings. Piston skirt coating, thermal coating on piston tops, etc, have come a long way.

I would also spend some time working on windage control. I believe there is probably some gains to be had in oil control with the long crank, slanted engine design, etc. Some work in oil drainback, via drain tubes back to oil pan, crankshaft scraper, and knife edge modifications to crank itself, might lead to some HP savings.