Production of cosmetic esters using an enzyme in place of traditional hazardous and energy intensive syntheses
Overview
Esters
are commonly used in cosmetics and other beauty products as emollients, emulsifiers
and skin-illuminators. They are traditionally synthesized via esterification
reactions of acyl compounds with alcohols. As the demand for natural beauty
products increases, companies are looking for beauty ingredients derived from renewable
resources.
Problem: Cosmetic esters are typically produced using
strong acids and high temperatures resulting in by-products that adversely
affect the yield and purity of the ester product. These side products require energy intensive
purifications that produce hazardous waste putting workers at risk and taxing
the environment.
Solution: Reactions catalyzed by enzymes such as
lipase work at low reaction temperatures, produce fewer by-products, and can
occur under solvent-free or aqueous reaction conditions. More pure esters can therefore
be generated from renewable resources meeting the desires of cosmetic and
personal care companies for natural beauty products.
Background
Table 1:
Top Selling Beauty Companies2
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Beauty Company
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Sales in 2016
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1
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2
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3
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4
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5
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Shiseido
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The cosmetic and personal care industry is
a multi-billion-dollar industry that is constantly expanding. Table 1 shows sales
in 2016 of the top 5 companies. L’Oréal,
had the highest sales in 2016, followed by Unilever (which includes popular
brands such as Dove, Degree, Axe and Suave) and Procter & Gamble (P&G).
Many of these companies have made recent changes towards sustainability with
their products and packaging. Not only does this movement help the environment,
but companies are satisfying the consumer demand for greener and more natural
products thus improving their public appeal.2 Cosmetic and personal
care companies are seeking ingredients derived from plants, micro-organisms, and
minerals that are isolated and purified from natural sources by safe and sustainable
methods.
Cosmetic
Esters
Esters are an
important group of beauty ingredients used as emulsifiers, emollients and
specialty active ingredients. Figure 1 shows some cosmetic esters commonly used
in a variety of beauty products. Emulsifiers
are “surface active compounds” that stabilize oil-water suspensions and are
typically found in creams and lotions. Emollients
are moisturizing ingredients that, when applied to the surface of the skin, prevent
water loss and moisturize dry skin.3 Emollients aid in the
absorption of other creams and oils but are not absorbed into the skin
themselves.3 The length of the carbon chain in the ester and the
degree of unsaturation, largely determine the performance of the ester and its physical
properties. Plant oils are ideal to derive cosmetic esters from because the
mixtures of fatty acids in plant oils will be mirrored in the mixture of
corresponding esters that are generated. The desired properties of an ester
mixture can therefore be achieved by choosing particular plant oils.
Traditional
Syntheses of Esters
Esters are
traditionally synthesized by hazardous and energy intensive processes such as
Fisher esterification reactions (Scheme 1). This is a condensation reaction of an
organic acid and an alcohol at high temperatures catalyzed by a strong
acid. The reaction is in equilibrium so in
order to obtain a high yield of the ester product, water is removed by
distillation forcing the reaction to the right according to Le Chatelier’s
principle. These harsh reaction conditions can destroy natural unsaturated
fatty acids such as linoleic acid (which is sensitive to oxidative degradation)
and create by-products that lower yields and generate waste which must be
removed by energy intensive purifications. Acid catalyzed trans-esterifications
can also be used to generate a specific ester in a manner similar to Fisher esterification
(Scheme 2). The reaction can be driven to product via distillation, if the alcohol
product has a lower boiling point than the reactant alcohol.
Esterifications accomplished
by reacting acid halides or anhydrides with alcohols (Scheme 3) are
irreversible processes. However, the reactions are expensive and involve reactive
acyl halides and anhydrides that must be synthesized prior to the reaction with
the alcohol. These
reactions require copious amounts of organic
solvents and require one equivalent of base, usually an amine, producing an
ammonium salt as waste that must be removed and disposed of.
Skin
Illuminating Ingredients
Some active
ingredients added in beauty products are used to even out and brighten skin
tone (Figure 2). These compounds work by inhibiting the enzyme tyrosinase which
is widely found in animals, plants, and microorganisms.4 The
activity of these compounds are represented by the EC50 value. This corresponds to the molar concentration at
which the tyrosinase exhibits 50% of its activity. The lower the value, the
more effective the inhibitor, meaning less of the ingredient is needed to obtain
the desired result. Kojic acid is the most common skin whitening ingredient
which is likely due to its effectiveness denoted by a very low EC50
value.4
Tyrosinase is an
enzyme important in the bio-synthesis of melanin from the amino acid tyrosine
in mammals. It uses molecular oxygen to oxidize o-diphenols to o-quinones
which eventually are turned into melanin.4 The generation of the
pigment melanin is a defense mechanism of the skin to protect itself from
ultraviolet (UV) radiation from the sun.4 The UV radiation creates
reactive oxygen species such as oxygen radicals which activate tyrosinase.4
Abnormal melanin pigmentation of the skin results in visible darks spots such
as freckles.4 Inhibition of tyrosinase therefore reduces the hyperpigmentation
of the skin caused by melanin giving the overall appearance of a more even skin
tone.
Green Chemistry
In 2005, Eastman started an investigation
using enzymatic bio-catalysts to produce cosmetic esters. The specificity of
enzymes and the gentle reaction conditions used are ideal to minimize
by-products and maximize the yield of the desired ester. Eastman demonstrated various
esters could be synthesized without organic solvents using enzymes such as
lipases. Lipases are classified serine
hydrolases which means they work by catalyzing the hydrolysis of esters or trans-esterification
reactions.5 As typical of many enzymes, lipases are stereoselective and
exhibit good activity.5 They have the ability to change
conformations in order to bind substrates of different sizes and orientations.6
Reactions catalyzed by lipases are performed at moderate temperatures, usually
< 60°C,
to prevent deactivation of the enzyme which occurs at temperatures above 100°C.6
The bio-catalytic process occurs according
to reaction in Scheme 4. The reaction is similar to the traditional synthetic methods
but in this case, the ester is activated by the enzyme releasing an alcohol and
an alcohol is added to create the desired ester regenerating the enzyme in the
process. The equilibrium is driven to product by removal of the alcohol by-product which can be done by several methods including distillation or chemisorption
on molecular sieves. Removing a product is preferred over adding excess of a
reagent in order to reduce waste and cost. Furthermore, an excess of organic
acid alters the pH of the system reducing enzyme activity and an excess of
alcohol can deactivate the enzyme.6
The
lipases are immobilized, usually on a solid resin, so the catalyst can be
easily handled and removed by filtration without compromising enzyme activity thus
allowing for its reuse.5 The process should require no further purification
after filtering resulting in a good yield of > 90% pure esters. The benefits
of this process include:
·
No
unwanted by-products are formed that could negatively impact the color or odor
of the product and must be removed by purification.
·
No
organic solvents are used eliminating trace amounts remaining in the final
product.
·
It
is estimated to save >10 L of organic solvents per 1 kg of product compared
to analogous esterification reactions performed with organic solvents.
·
Enzymes
can be reused until they become permanently deactivated but are ultimately
bio-degradable.
·
Hazardous
reagents, such as sulfuric acid, are eliminated making the manufacturing
process safer.
·
Running
the reaction at mild temperatures reduces energy usage.
This bio-catalytic process has been used
to generate cosmetic esters from natural ingredients such as rice bran oil
(which creates esters used as emollients) and vegetable glycerin (which
produces glyceride esters for emulsifiers). It has also been used to make unique natural esters including
glyceryl pomegranate (from pomegranate seed oil) and glyceryl passionate (from
passionflower seed oil) with >95% purity. Both of these products are similar
to glyceryl stearate (Figure 1). These esters are produced simply by reacting
fatty acid mixtures from natural oils with glycerin (Figure 4) and the
bio-catalyst.
The bio-catalytic process has also been used
to form effective tyrosinase inhibiting esters. The compound 4-hydroxy benzyl
alcohol (4-HBA) (Figure 5), which is structurally related to kojic acid (Figure
2), has shown potential for evening out skin tone. Upon traditional
esterification of 4-HBA, the phenol alcohol is preferentially transformed
producing 4-HBA acetate. Enzymatic
esterification of 4-HBA is highly selective for the primary benzyl alcohol (>98%).
In comparison, the EC50 value of the enzymatic product shows it is a
much more selective tyrosinase inhibitor than the traditional method product.
Fatty acid esters of kojic acid have shown
increased skin permeability as well as pH and thermal stability making them
ideal for natural and effective skin illuminating ingredients. It is proposed
that fatty acid esters of 4-HBA will have a similar increase in their
effectiveness and stability. This opens doors for further uses of this
enzymatic process to create highly active skin illuminating ingredients derived
from natural fatty acids and 4-HBA.
Green Chemistry in
Action
Eastman’s bio-catalytic process for
esterification can produce hundreds of high purity cosmetic esters. Their
bio-catalytic process and natural esters were featured in major industrial trade shows
in 2008. The selectivity and flexibility of the catalytic process allows
cosmetic companies to create designer esters from countless natural materials
and brand their own unique ingredients. This innovation is accomplished in an energy
and cost-efficient manner while reducing the environmental footprint of producing
cosmetic esters.
References
1.
This case was based upon the work of Eastman
Chemical Company from their Presidential Green Chemistry Challenge award
proposal for a solvent-free biocatalytic process for cosmetic and personal care
ingredients.
2.
Ilchi, Layla. “WWD Beauty Inc.'s Top 10
Beauty Companies of 2016.” WWD, 13 Apr. 2017,
wwd.com/beauty-industry-news/beauty-features/gallery/wwd-beauty-inc-s-top-10-beauty-companies-of-10864705/.
"Emollients." NHS Choices. NHS UK, 18 June 2012. Web. 15 May
2014.
3.
Matsuura, Ritaro, Hiroyuki Ukeda,
and Masayoshi Sawamura. "Tyrosinase Inhibitory Activity of Citrus
Essential Oils." Journal of Agricultural and Food Chemistry 54.6
(2006): 2309-313. ACS. Web. 18 May 2014.
4.
Cordova, Armando, and Kim D. Janda.
"A Highly Chemo- and Stereoselective Synthesis of β-Keto Esters via a
Polymer-Supported Lipase Catalyzed." Journal of Organic Chemistry
66.5 (2001): 1906-909. ACS. Web. 20 May 2014.
5.
Arroyo, Miguel, and Jose Sinisterra.
"High Enantioselective Esterification of 2-Arylpropionic Acids Catalyzed
by Immobilized Lipase from Candida Anturctica: A Mechanistic Approach." Journal
of Organic Chemistry 59.16 (1994): 4410-417. ACS. Web. 20 May 2014.
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