The Power of Chemistry: Natural versus
Synthetic Compounds
by Theresa Beaty, Ph.D.
Indigo is the dye that makes the “blue” in blue jeans. It has
been used for thousands of years to color textiles. Some civi-
lizations have also used indigo in paint and cosmetics. Until
the late 1800s, indigo was produced from plant sources on
tropical plantations, mainly in India. In fact, the name indigois
derived from India. After harvesting the Indigoferaplants,
workers on the indigo plantations spent many days preparing
just one batch of the dye. The plants were soaked in water to
extract the colorless compound, indecan. This mixture was
fermented for up to 15 hours, during which the indecan was
converted into indoxyl. This yellow liquid was agitated while
the color changed to green and then blue. Dark flakes were
formed, and the mixture was boiled to remove impurities. The
flakes were filtered and pressed to remove moisture, then cut
into cubes and air-dried. This dried indigowas ready for mar-
ket. Because of the lengthy processing required to produce
the dye, indigo was very expensive.
During the last half of the 19th century, organic chemists
discovered how to synthesize different dyes in the laboratory.
Although some of the chemical steps involved in the synthesis
reactions were complicated, these synthetic dyes were still
much cheaper than the natural dyes isolated from plants or
shellfish. The chemical synthesis of indigo was first published
in 1882. This chemical reaction started with o-nitrobenzalde-
hyde, a component of coal tar. Acetone was added under
basic conditions (dilute NaOH), and the resulting compound
formed a dimer, indigo.
This initial synthesis reaction was modified in the late
1890s for large-scale commercial production. It required
petroleum-based starting reagents and generated toxic by-
products. However, synthetic indigo was easier to produce
than natural indigo, and therefore cheaper. The synthetic
dye became increasingly popular. By World War I, nearly all
of the indigo sold on international markets was synthesized
in laboratories.
The effects of synthetic indigo on society were more
widespread than one might think. Synthetic indigo was not
merely the cheaper source of dye. It also contributed to the
eventual independence of India from the British Empire.
Because the process of generating natural indigo was so
labor-intensive, thousands of workers were affected when the
plantations became too expensive to efficiently operate during
the early 1900s. The plantation workers had to work longer
hours in order to try and produce more natural indigo. Since
most of the plantations were in India, this contributed to the
social and political unrest in that country. Mahatma Gandhi
was one of the leaders who used the terrible conditions on the
plantations as a means to organize the Indian population to
protest British rule. Thus, the economic turmoil caused by the
chemical synthesis of indigo contributed to the efforts of the
Indian people to become independent of Great Britain.
While synthetic indigo has enjoyed a virtual monopoly for
nearly a century, another method for generating an environ-
mentally friendly indigo is under development. At the end of the
20th century, the enzymes required for cellular indigo synthesis
were cloned into bacteria. When these genetically modified
bacteria are fed tryptophan, they synthesize indigo and secrete
it into the growth medium. This bioindigo is not yet economical
because the bacteria produce it so slowly. However, scientists
continue to enhance the growth conditions of these biological
indigo factories. Perhaps one day, the “blue” in blue jeans will
be primarily produced by genetically engineered bacteria.
Besides indigo, many other natural products have been
produced in the laboratory. One of these is quinine, a com-
pound used for hundreds of years to treat malaria. Quinine is
naturally derived from the bark of the tropical Cinchonatrees
found in Amazonia. Chemists had been trying to synthesize
this important drug since the mid-1800s, and finally suc-
ceeded in the 1940s. The availability of synthetic quinine
helped the Allied troops combat malaria in the Pacific during
World War II, and thus it may indirectly be partly responsible
for the outcome of the war.
Another compound derived from bark, this time from the
Pacific yew tree, is paclitaxol, better known as Taxol. This
drug has potent antitumor activity. However, each yew tree
makes so little of the compound that the bark of several old
trees is required to treat just one cancer patient. Since har-
vesting the bark kills the tree, there is a tremendous drive to
generate a high-yield synthesis reaction for Taxol. While the
compound was first synthesized in the laboratory in the 1990s,
the yields are too small to be practical. Chemists are continu-
ing to work on a better synthesis pathway for this drug. In
addition, derivatives of Taxol are being created that may have
even more potent anticancer activity.
Other natural products that have synthetic or semisyn-
thetic versions include antibiotics, antifungals, and anesthetics.
Creating synthetic versions of useful natural products
certainly benefits society by producing cheaper compounds.
However, synthetic chemistry can also be environmentally
friendly. Improved synthetic pathways can reduce the amount
of toxic by-products formed during some chemical reactions.
In addition, the availability of synthetic compounds eliminates
the need to continually harvest large quantities of rare plants
or other organisms in order to isolate the natural product.—Theresa Beaty, Ph.D.,is an associate professor
in the department of chemistry & physics at
Le Moyne College in Syracuse, New York.configuration (electronic) 57