New synthetic connections have been established between
glucose and aromatic chemicals such as
pyrogallol,
hydroquinone, and
resorcinol. The centerpiece of this approach is the removal of one
oxygen atom from 1,2,3,4-tetrahydroxybenzene,
hydroxyhydroquinone, and
phloroglucinol methyl
ether to form
pyrogallol,
hydroquinone, and
resorcinol, respectively. Deoxygenations are accomplished by Rh-catalyzed hydrogenation of the starting polyhydroxybenzenes followed by
acid-catalyzed
dehydration of putative dihydro intermediates.
Pyrogallol synthesis consists of converting
glucose into myo-
inositol, oxidation to
myo-2-inosose,
dehydration to 1,2,3,4-tetrahydroxybenzene, and deoxygenation to form
pyrogallol. Synthesis of
pyrogallol via
myo-2-inosose requires 4
enzyme-catalyzed and 2 chemical steps. For comparison, synthesis of
pyrogallol from
glucose via
gallic acid intermediacy and the
shikimate pathway requires at least 20
enzyme-catalyzed steps. A new
benzene-free synthesis of
hydroquinone employs conversion of
glucose into
2-deoxy-scyllo-inosose,
dehydration of this
inosose to
hydroxyhydroquinone, and subsequent deoxygenation to form
hydroquinone. Synthesis of
hydroquinone via
2-deoxy-scyllo-inosose requires 2
enzyme-catalyzed and 2 chemical steps. By contrast, synthesis of
hydroquinone using the
shikimate pathway and intermediacy of
quinic acid requires 18
enzyme-catalyzed steps and 1 chemical step. Methylation of
triacetic acid lactone, cyclization, and regioselective deoxygenation of
phloroglucinol methyl
ether affords
resorcinol. Given the ability to synthesize
triacetic acid lactone from
glucose, this constitutes the first
benzene-free route for the synthesis of
resorcinol.