Exposure to benzene, which has been linked to acute myeloid leukemia and non-Hodgkin's
lymphoma, is a continuing problem for the chemical industry.
The most effective way of dealing with benzene's human
health risk is to eliminate its use. Such a far-reaching
solution requires the elaboration of fundamentally new
syntheses for chemicals derived from benzene. Along these
lines (Scheme 1), we have elaborated syntheses of phenol,1
catechol, hydroquinone,2 pyrogallol,3
acid 5 and caprolactam where
benzene is replaced as a starting material with nontoxic
glucose. Considerable research activity is currently being
focused on elaboration of syntheses of phloroglucinol
and resorcinol from glucose.
Our benzene-free synthetic routes typically
entail microbial synthesis of an intermediate followed
by chemical conversion of this intermediate into the desired
product. Examples of this strategy are found in our syntheses
of phenol1 and hydroquinone,2
which are highly toxic to microbes. The microbial toxicity
of phenol is circumvented by high-yielding microbial synthesis
of nontoxic shikimic acid, which can be accomplished using
recombinant strains cloned in our group (Scheme 2). 6,
7, 8 Shikimic acid is then heated in near-critical
water to afford phenol (Scheme 2).1
Synthesis of hydroquinone begins with the high-yielding
microbial synthesis of quinic acid using a recombinant
strain cloned in our group (Scheme 2).2
Nontoxic quinic acid is then chemically converted into
hydroquinone (Scheme 2). The chemical methodology employs
either NaOCl, which is arguably the world's cheapest stoichiometric
oxidant, or catalytic amounts of Ag+1
with K2S2O8 serving as the cooxidant.2
(a),(b),(c),(d) recombinant microbes; (e) H2O,
350 °C; (f) NaOCl or Ag+1/K2S2O8; (g) chemical deamination/cyclization;
H2, Pt on C.
Synthesis of bionylon has been another research
goal. The nylon market is dominated by nylon 66 and nylon
6, which are respectively produced from adipic acid and
caprolactam. Global production of adipic acid is approximately
2.0 x 109 kg/yr. Our synthesis of adipic acid (Scheme
2) begins with the construction and use of a recombinant
microbe that catalyzes the conversion of glucose into
cis,cis-muconic acid.5 Hydrogenation of cis,cis-muconic
acid affords adipic acid in quantitative yield (Scheme
2).5 Global production of caprolactam is approximately
3.6 x 109 kg/yr. Improvements in the yield of L-lysine
microbially synthesized from glucose coupled with the
increased demand for this amino acid suggest that L-lysine
could be an attractive starting material for production
of caprolactam. Using synthetic organic methodology developed
in our group, we are currently achieving a 60% (mol/mol)
yield of sublimed caprolactam from L-lysine (Scheme 2).
In addition to its problematic toxicity,
benzene contributes significantly to the profitability
of petroleum production and refining. The majority of
the petroleum used by the United States is now imported
and leads to geopolitical problems. Specifically, reliance
on politically unstable countries for petroleum imports
has played a significant role in the rise and spread of
anti-American fervor and global terrorism. By contrast,
glucose is derived from renewable starch and cellulose,
which are produced in great abundance in the United States.
Starch and cellulose are also essentially immobilized
CO2. As a consequence, synthesis
of chemicals, particularly large-volume commodity chemicals,
from glucose is essentially a method for immobilization
of atmospheric CO2. Such a credit,
even if initially modest, may be critical as the United
States belatedly struggles to meet national CO2
budgets set by international treaty.
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