EXOTIC POSSIBILITIES R&D brings to consumers taste and scent experiences they might never encounter otherwise. TAKASAGO PHOTO

Flavors and fragrances enhance life. A world with limited tastes and smells would be bleak and boring. As consumers clamor for more pleasing, more convenient, and more functional products, the flavor and fragrance industry ensures a constant infusion of new experiences to surprise and please the chemical senses, even as it grapples with price pressures and regulations.

Discovery is the fountain from which new ingredients, flavors, fragrances, and eventually consumer products flow. The most common approach to discovering new ingredients is to prepare variants of known compounds and evaluate their efficacy. Modeling techniques are enhancing this activity.

For example, fragrance researchers at Givaudan have developed models for odor types--or "notes"--by using molecular modeling software. Working from known compounds with the characteristic fragrance note, the software generates a three-dimensional model of the common structural features. New structures are juxtaposed onto the model. If the fit is good, the compound is prepared and evaluated.

Givaudan chemist Jerzy A. Bajgrowicz and coworkers recently used this approach to invent new compounds with a so-called green/galbanum note [Bioorg. Med. Chem., 11, 2931 (2003)]. This fragrance is characterized by a green, slightly spicy, fruity odor. Earlier, the same technique led to compounds with a potent amberlike odor [Tetrahedron: Asymmetry, 12, 2049 (2001)].

"Very often, chance helps whatever rational approach we're pursuing," says Georg Fráter, head of Givaudan's research center in Dübendorf, Switzerland. A recent example is the doubly cyclopropanated sandalwood odorant Javanol. "During synthesis of a potential sandalwood substitute, chemists were surprised [to find that] the unusually strong and diffusive natural sandalwood scent of the crude reaction mixture was not due to the target compound but to a by-product," he explains. Javanol has since been commercialized. Givaudan prepares it from a-pinene.

One goal is to invent more intense and more long-lasting alternatives to known odorants. Increasingly, the industry has to deal with environmental and health issues and regulations. "A fantastically powerful compound--one that can satisfy global demand in kilogram quantities rather than ton quantities--can address many of those problems," Fráter says. Low volume means less impact on health and the environment and simpler registration, he explains.

PREDICTING ODORANTS Potential new fragrance compounds are tested against a computer-generated model of an olfactophore. J. A. BAJGROWICZ/GIVAUDAN

NATURE CONTINUES to be a great resource. Givaudan is well known for its fragrance-hunting expeditions, led by Roman Kaiser, a distinguished research fellow and director of natural scents at Givaudan. Called ScentTrek, these expeditions have taken Kaiser and others to the tropical rain forests of French Guyana, Gabon, Madagascar, South Africa, and Papua New Guinea, where they search for new "fragrance concepts."

"Nature provides new combinations of individual ingredients," Kaiser says. "Sometimes we find scents that are familiar but unusual because the ratios of components are new or because they contain a new scent molecule. We find surprising scents with combinations that perfumers would never have considered."

During these expeditions, sampling is by nondestructive methods only, Kaiser says. For example, during the most recent trip to southern India, headspace samples were collected from about 40 species of plants. "Each sample is 100 mg, so we took only about 4 mg [total] of material," he says. Back in the lab, the trapped scents are analyzed, usually by gas chromatography and mass spectrometry. The results enable chemists to reconstitute unusual natural scents.

In terms of finding new compounds that can be commercialized, ScentTrek is high risk, with a success rate of about one every two years, Kaiser says. But the reconstituted scents, which are used in many fine fragrances, give Givaudan an edge, he says. "It's important to have a big collection, because trends change and you have to be ready to give perfumers building blocks for new creations as quickly as possible."

Recent discoveries of human taste and odor receptors offer another route to discovery. Receptors can be reconstructed in cell lines that can be used for rapid screening of large numbers of taste or odor compounds, says Robert G. Eilerman, senior vice president for flavor R&D at Givaudan Flavors, Cincinnati. Receptors sensitive to heat and cold are also of interest, as are fat receptors that signal satiation. "This approach is potentially a better way to identify materials that elicit specific effects," he adds.

Kaiser's expeditions have encouraged Givaudan researchers to hunt for flavors around the world. Destinations include not only remote rain forests but also local restaurants in Asia.

Unlike fragrances, which can have global appeal, flavors are much more grounded in geography. "To be successful, a flavor typically has to resemble something people already know," says Charles H. Manley, vice president for science and technology at Takasago International Corp.

That's why Japanese confections, which usually are not very sweet, are not popular with U.S. consumers. That's also why the fish sauce widely used in Southeast Asian cuisines can smell disgusting to those unfamiliar with it.

FRAGRANCE HUNTER At the Masoala Peninsula of Madagascar, Kaiser encountered gleaming white flowers of a close but little-known relative of Stephanotis floribunda at the peak of their visual and olfactory beauty. GIVAUDAN PHOTO
CUISINE CHEMISTRY The headspace of regional dishes while being prepared reveals interesting flavor compositions. GIVAUDAN PHOTO

IMMIGRATION AND TRAVEL have bridged lands and peoples. Indonesian restaurants are popular in Amsterdam; Indian restaurants, in London. They serve not only the Dutch or the British who have acquired the tastes of their former colonies, but also the Indonesians and Indians who have immigrated to the lands of their former colonizers but yearn for the tastes of their native homelands. Meanwhile, rising standards of living are enabling more and more consumers in developing countries to eat at restaurants and buy snacks, toothpaste, beverages, microwave dinners, and other flavored products.

Givaudan's flavor-hunting trips, called TasteTrek, have yielded about 50 potential new flavor compounds, Eilerman says. One of these trips brought a Givaudan team to a market in Libreville, Gabon, where they realized that the Gabonese use tree barks as a food spice. The barks smell like onion or garlic. Headspace analysis of the aroma revealed a multitude of sulfur-containing compounds, but the characteristic odor is due mainly to only two: 2,3,5-trithiahexane and 2,4,6-trithiaheptane. "We have used chemicals identified from that bark to create some unique vegetable flavors," Eilerman says.

An expedition to China led to a new flavor ingredient, captured from meals being prepared in a restaurant. According to an account of the trip, the sampling, made possible by a portable laboratory with headspace-sampling gear, attracted curious stares from restaurant customers. The flavor ingredient, now commercialized, is called Wok Aroma.

Compounds that behave in a certain way to impart a particular effect are another target of discovery. For example, Givaudan has designed odorless compounds that when exposed to sunlight react to produce odorants. They are used to give a pleasant scent to freshly dried laundry, Fráter says. Among these are o-hydroxycinnamates in which the alcohol is an odorant. When exposed to sunlight, the odorless trans ester isomerizes to an unstable cis ester, which cyclizes, forming coumarin and releasing the alcohol.

Manufacturing routes are designed for producing successful compounds from discovery efforts. Although the industry relies on suppliers for most raw materials, unique, proprietary ingredients usually are manufactured in-house. Increasingly, the industry is turning to fermentation because of the demand for natural ingredients. Fermentation-derived compounds, which are considered natural, usually are less expensive than isolates from plants or animals.

A recent example from International Flavors & Fragrances (IFF) is a method to prepare styrallyl alcohols by fermentation of acetophenone. The alcohols are converted to styrallyl acetate by what Markus Eckert, director for natural products and technology, refers to as natural synthesis--that is, using natural starting materials (natural styrallyl alcohol and natural acetic acid) and processing conditions considered natural, such as kitchen-cooking conditions.

Styrallyl acetate has a powerful green odor and is used in various fruit flavors and in fruity and floral fragrance compositions. Although synthetic styrallyl acetate is widely available, IFF developed the fermentation process in response to requests from IFF flavorists and perfumers for a natural version, Eckert says.

WHAT'S MORE TYPICAL is to design synthetic routes to compounds traditionally derived from natural sources. A recent example comes from Ube Industries, which has developed a process for -methyl-1,3-benzodioxole-5-propanal (MDP) based on nonnatural raw materials. According to Yoshinori Kawai, a director at Ube America, MDP is a fragrance component characterized by a unique marine aroma. Demand for the compound is estimated at 1,000 tons per year, and various fragrance companies supply the material under different trade names.

Most of the MDP in the market is based on safrole, which comes from the tree Sassafras officinalis. "The supply and quality of the raw material is not stable, and the growing demand for MDP is causing deforestation," Kawai says. "For these reasons, a manufacturing process based on easily available raw materials has been awaited." Ube's process, based on catechol, is shorter than routes based on safrole. The product will be available in 2004 under the trade name Heliofresh, Kawai adds.

Although flavors and fragrances share a significant number of raw materials, collectively called aroma chemicals, flavorists and perfumers work under different constraints. Fragrances play on emotions, and perfumers can indulge flights of fancy. To satisfy hunger or whet the appetite, flavors must be familiar, so flavorists have less creative license.

An inquiry for a new fragrance can be as minimal as an idea--for instance, Michael Jordan. On the other hand, according to John W. Knoop, a U.K.-based flavor consultant, inquiries for new flavors are more direct, usually in the form of "match the flavor of Coca-Cola" or "create a new soft drink to compete with Coca-Cola." The first seeks perhaps a low-cost alternative to Coca-Cola; the second, a product to overtake Coca-Cola as the most widely consumed beverage in the world. Both types of inquiries are common, he says.

Nevertheless, Knoop says he has heard of a flavor inquiry that seems more typical for fragrances: a soft drink for a formula-one motor-racing team. In this case, he explains, the flavorist first must look at motor racing, the types of people interested in the sport, and the kind of drink that will capture the sport.

Although Knoop himself specializes in savory flavors, he describes how he might go about addressing this inquiry: "A fruity note would be too light. I can see a lot of people interested in motor racing as being more likely to drink alcoholic beverages. Spicy would be my link to the sport. I would probably go for something based on ginger, possibly with some clove, for a fatty note to associate with the oil in motor racing."

Whatever flavorists or perfumers create must pass another hurdle: Will it work in the end product? Applications research is about answering this question.

Many things can go wrong with flavored or fragranced products. Flavors must survive acidic pH in a beverage, be inert to transformations by bacteria in yogurt, or withstand heat during processing. Fragrances must stick to fabrics if used in laundry products, resist harsh chemicals if used in toilet bowl cleaners, or release fragrance slowly if used in room deodorants.

The complexity of these problems has made R&D more interdisciplinary than before. Fráter notes the increasing involvement of physical chemists, to study complex systems such as the washing-machine environment, and of polymer chemists, to stabilize vulnerable compounds through encapsulation.

The industry is committed to enhancing the human sensory experience. The flavor side is facing new challenges with functional foods, such as soy-based products. "Most functional products don't have a pleasant taste," Manley says. "Some people buy soy products for the health claims only, but in the end, most people buy if they like the taste of it. If a product has both good taste and health benefits, it's a winner."

The same could be said for vegetarian products. "They used to be bad; the texture was not right, and they didn't taste good," Eilerman says. "Protein processors now have better ways to build in texture, and we now know how to flavor them in a more sophisticated way."

On the fragrance side, innovative uses are being explored. In Europe, according to Fráter, a much-discussed idea is the scented cinema, in which odors related to screen images are released at the appropriate moment. For example, an advertisement for coffee would be accompanied by a coffee aroma enveloping the space. Execution requires much physical chemistry and engineering, he says. "The molecules must be released in a controlled manner within a certain time. Then the odor must be removed quickly to make way for the next one."

Last year, Kaiser did something along these lines at the Lucerne Festival, an annual concert festival held in Lucerne, Switzerland. "The theme was seduction, and the organizers asked if we could contribute fragrance to one of the concert evenings," he tells C&EN. Givaudan agreed to complement with fragrances the evening designated Oriental Night, in which Scheherazade by Nikolay Rimsky-Korsakov would be performed.

The music tells a story, and Kaiser selected scents to represent the principal characters. For the sultan, he composed an agarwood-based scent with ambery, musky, and "animalic" character to suggest softness and sensuality as well as aggressiveness. For Scheherazade, he chose the floral scent of Aglaia odorata, which is mild. But it was delivered to quickly fill the concert hall so that in the end it prevailed over the agarwood scent, just as Scheherazade prevailed over the sultan, he says.

The fragrances got mixed reviews. The musicians found it stimulating, Kaiser says. "With the public, the reaction depended very much on how well a person is informed. The program explained what was going to happen. But not everyone reads programs. Those who were aware enjoyed the olfactory experience. Those who were unaware were indifferent."

And currently, in the Swiss canton of Schwyz, the Swiss National Museum is presenting an exhibit called the "Scents of the Alps." For this, Kaiser reconstituted alpine flower scents. "When you smell them, you can experience the odors encountered while hiking in the Swiss Alps," he says.

"I don't think a lot of chemistry graduates know about the flavor and fragrance business," Eilerman comments. "I hope more people will be interested. Chemistry is not just about pharma and petroleum. There are other areas out there that are fun and rewarding, too."

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Copyright © 2003 American Chemical Society