Synthesis of Caged HMG-CoA Reductase Substrates for the Elucidation of Cellular Pathways.

The synthesis of photocaged substrates of the biologically important enzyme HMG-CoA reductase is reported. HMG-CoA bearing a -hydroxyphenacyl (pHP) photocage moiety was synthesized in an overall yield of 14% over seven steps in addition to caged forms of mevalonate and mevaldehyde. The absorption maximum and quantum yield for the decaging of the photocaged compounds are dependent on pH with a λ of 330 nm and a ϕ of 5%, respectively, at pH 9.1 but a λ of 290 nm and a ϕ of 16%, respectively, at pH 6.7.