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

The synthesis of photocaged substrates of the biologically important enzyme HMG-CoA reductase is reported. HMG-CoA bearing a p-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 decaging of the photocaged compounds is pH dependent with a lambda (max) = 330 nm and a quantum yield of 5%, respectively, at pH 9.1 but lambda (max) = 290 nm and a quantum yield of 16% at pH 6.7.