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The major focus of IFF’s research pursuits has been to develop unique, proprietary fragrance molecules which enhance the creativity of IFF's perfumers. Development of innovative fragrance ingredients such as Galaxolide®, Iso E super®, Lyral®, Helional®, Cashmeran®, Kharismal®, Cassiffix®, Bacdanol®, Montaverdi®, Trisamber® and many more have allowed IFF to create many legendary perfumes for IFF's global customers. As a part of the continuing leadership in the area of new molecules, we at IFF are always pushing the art of perfumery and synthesis. One such area is the study of Chirality and odor. Therefore, efforts have been underway to delineate odor differences among IFF's patented and captive fragrance ingredients which possess optically active centers.
It is well known that chirality can, in some instances, dramatically influence odor perception between optically pure and racemic compounds. Therefore, odor evaluation of chiral materials is an essential part of the discovery process at IFF. Analytical techniques such as GC CHARM Analysis® used by IFF R&D have enhanced odor evaluation and odor threshold determination. Additionally, IFF is evaluating the technical challenges associated with having chiral isomers of key fragrance ingredients odor evaluated. There exist two basic approaches to odor evaluating racemic fragrance ingredients. The first is to design specific chiral syntheses for each specific isomer. This methodology is best practiced on molecules with one or two chiral centers. The second approach is to utilize gas chromatography. Odor evaluation utilizing GC instrumentation has been employed in the industry for more than twenty years. The idea is to couple chiral GC separations and GC sniffing to odor evaluate specific enantiomers.
The initial plan will focus on the proprietary 4,4a,5,6,7,8,9,9b-octahydro-7,7,8,9,9-pentamethyl indeno[4,5-d]-1,3-dioxin. A material with eight enantiomers outlined in table 1. Analytical separation of the isomers is the first course of action using chiral GC column(s). When conditions have been developed to resolve the eight isomers the column can be transferred to an instrument equipped for GC sniffing. In this way odor description and relative threshold information can be obtained for each isomer. The challenge will be linking the chiral isomers and the odor evaluations. To conclusively match the structure and the chiral GC retention time chiral synthesis may be necessary. To carry out chiral synthesis extensive literature searching and evaluation will be required to identify reliable synthetic methods to make the desired chiral target molecules.
Table 1
 | 4aR, 9bR, 8R-Z
4aS, 9bS, 8S-Z | 4aR, 9bS, 8S-Z
4aS, 9bR, 8R-Z |
 | 4aR, 9bR, 8S-Z
4aS, 9bS, 8R-Z | 4aR, 9bS, 8R-Z
4aS, 9bR, 8S-Z |
Z= 4,4a,5,6,7,8,9,9b-octahydro-7,7,8,9,9-pentamethyl-indano[4,5-d]-dioxin.
After developing a protocol to evaluate the chiral isomers of 4,4a,5,6,7,8,9,9b-octahydro-7,7,8,9,9-pentamethyl indeno[4,5-d]-1,3-dioxin the technology will be extended to patented 2,2,6,6,7,8,8-heptamethy-decahydro-2H-indeno[4,5-b]furan. This is significantly more challenging because this molecule contains five chiral centers affording thirty two enantiomers. The possible chiral combinations are outlined in table 2.
Table 2
1R, 2R, 6R, 9R, 11R-Z
1S, 2S, 6S, 9S, 11S-Z
1S, 2R, 6R, 9R, 11R-Z
1R, 2S, 6S, 9S, 11S-Z
1R, 2S, 6R, 9R, 11R-Z
1S, 2R, 6S, 9S, 11S-Z
1R, 2R, 6S, 9R, 11R-Z
1S, 2S, 6R, 9S, 11S-Z
1R, 2R, 6R, 9S, 11R-Z
1S, 2S, 6S, 9R, 11S-Z | 1R, 2R, 6R, 9R, 11S-Z
1S, 2S, 6S, 9S, 11R-Z
1S, 2S, 6R, 9R, 11R-Z
1R, 2R, 6S, 9S, 11S-Z
1R, 2S, 6S, 9R, 11R-Z
1S, 2R, 6R, 9S, 11S-Z
1R, 2R, 6S, 9S, 11R-Z
1S, 2S, 6R, 9R, 11S-Z
1R, 2R, 6R, 9S, 11S-Z
1S, 2S, 6S, 9R, 11R-Z | 1S, 2R, 6S, 9R, 11R-Z
1R, 2S, 6R, 9S, 11S-Z
1S, 2R, 6R, 9S, 11R-Z
1R, 2S, 6S, 9R, 11S-Z
1S, 2R, 6R, 9R, 11S-Z
1R, 2S, 6S, 9S, 11R-Z
1R, 2S, 6R, 9S, 11R-Z
1S, 2R, 6S, 9R, 11S-Z
1R, 2S, 6R, 9R, 11S-Z
1S, 2R, 6S, 9S, 11R-Z
1R, 2S, 6R, 9S, 11R-Z
1S, 2R, 6S, 9R, 11S-Z |
Z= 4,4,10,10,11,12,12-heptamethyl-3-oxatricyclo[7.3.0.0<2,6>]-dodecane
Currently chiral fragrance ingredients are either derived from the chiral pool such as alpha pinene or prepared using a single asymmetric reaction like chiral hydrogenation. Having the capability to odor evaluate chiral isomers by GC sniffing IFF can determine the perfumery value of each enantiomer. Such evaluations support research efforts to design and develop chiral fragrance ingredients by introducing new chemical technologies specifically geared to asymmetric synthesis at selected IFF manufacturing locations. The result of this type of research will be the identification of, as of yet unknown, chiral proprietary fragrance ingredients.
Authors:
Anthony Levorse Ph.D.
Research Fellow
IFF R&D
Anubhav Narula Ph.D.
Sr. Research Fellow
IFF R&D
Posted on August 28, 2008 |
