May 5, 2003
Volume 81, Number 18
CENEAR 81 18
ISSN 0009-2347

History and choice shape portfolios

Creating a technology portfolio is never a perfect process. Many companies carry baggage that dictates some decisions, and as the following excerpts show, chiral chemistry portfolios have been shaped both by historical circumstance and by choice.

Ellen M. de Brabander, senior vice president for global R&D, DSM Pharmaceutical Products:

"We have grown very fast, largely through acquisitions. Every acquisition brought its own chiral technology. We started in 1987 with a company known for classical resolutions, Océ-Andeno. In 1998, we acquired Gist-brocades, which brought fermentation expertise. This strengthened our existing position in biocatalysis. We knew how to apply biocatalysts, and the Gist-brocades people knew how to discover and screen biocatalysts. The technologies were very complementary.

"In 2000, DSM acquired Catalytica Pharmaceuticals. Their strength in homogeneous catalysis complemented our own position in this field, which we had established even before the acquisition. The Catalytica people were focusing especially on asymmetric hydrogenation and epoxidation, which were nice fits from the technology point of view.

"Last February, we acquired a minority share in Syncom. This contract-research company is well known for its chiral expertise, and we have been collaborating with them for many years. They are the inventors of the Dutch resolution technology.
"Right now we are satisfied with our technology portfolio. Global competence managers in fields key to chiral chemistry are monitoring what's going on in those areas."

Karlheinz Drauz, vice president for technology and R&D management, Degussa:

"Our position in biocatalysis comes from 40 years of working in the area of amino acids, as well as coinvestigations with academic partners. For example, we have been examining ways to change enzyme enantioselectivity with Frances H. Arnold at California Institute of Technology.

"We also have proprietary catalytic systems to access chiral molecules for which no better, or other, method is available. These have come about through internal R&D, usually in collaboration with academic groups. Most are for asymmetric hydrogenations.

"In 2001, we acquired a research organization from the old Hoechst company, called Aventis Research & Technology. This was a group of around 30 highly specialized and well-equipped people whose main business was to screen, test, and develop homogeneous metal catalysts. They are now part of Degussa's Project House Catalysis.

"We are starting to develop biocatalytic asymmetric carbon-carbon bond-forming reactions. We also have metal catalysts for metathesis reactions, which came from the Aventis R&T package."

Ian C. Lennon, technology leader, Dowpharma:

"A majority of Dowpharma's chiral technology came along with Chirotech in the acquisition of Ascot in 2001. Chirotech's origins can be traced back to 1987 in a company called Enzymatix, which produced enzymes for chiral resolution and other applications. Enzymatix broke up in 1992, and the enzymes for fine chemicals--the lipases and the amidases for chiral resolutions--went to a new company called Chiros.

"Chiros expanded its chemistry by adding classical resolutions to its biocatalysis repertoire. In 1994, Chiros became Chiroscience and added drug discovery to the existing technology outfit that was supplying chiral intermediates produced by resolution with enzymes or chiral pool starting materials.

"Soon we recognized the need to add chemocatalysis. Resolutions would be less effective for the more complex molecules coming through the pipeline. This led in 1995 to the DuPhos license, our first big inlicense of chiral chemocatalysis technology. After we obtained the license, Mark J. Burk, the inventor of Duphos, joined us and helped us develop our hydrogenation capability. Also in 1995, I spent six months working in the lab of Barry M. Trost at Stanford University to assess his palladium technology for allylic alkylation.

"Around this time, it became evident at Chiroscience that we had a conflict in serving customer needs between the drug discovery side and the service side of the business. In 1996, Chiroscience formed a technology service business, which formally became Chirotech in 1998.

"Chirotech continued to add to its technology portfolio. We licensed the Trost palladium technology in 1997 and the Trost molybdenum technology for asymmetric allylic substitution in 1998; in 1999, we obtained a license from Merck for the Phanephos ligand; in 2000, we secured a license for the Noyori ketone reduction technology from the Japan Science & Technology Corp.

"Hydrogenation really is our flagship in-house technology, and we have been adding new ligands to our collection on a regular basis: Ferrotane, Hexaphemp, and Ph-BPE.

"In 1998, Chiroscience sold a minority stake in Chirotech to Ascot. In 1999, Ascot bought the rest of Chirotech. And in 2001, Ascot was bought by Dow Chemical.

"Since then, we have continued to grow our chiral technology portfolio. We licensed the Trost aldol technology last year, and just recently, working with Dow's process chemists in South Charleston [W.V.]--formerly Union Carbide--and Midland [Mich.], we have come up with a range of chiral rhodium-based catalysts for hydroformylation of a wide range of substrates."

Ralf Pfirmann, global business director for Clariant's pharmaceutical business unit:

"Clariant has always had a strong position in organic reductions, and it was natural to extend this strength to chiral reductions. As a backup to the in-house expertise we have developed, we have arranged for access to the pool of asymmetric hydrogenation ligands of Chiral Quest.

"We make chiral cyanohydrins from aldehydes, which can be transformed to many types of chiral building blocks. This is based on Clariant's strength in oxidations, which allow access to the aldehyde and ketone starting materials. Our classical portfolio includes all kinds of aldehydes. As chance would have it, we had been working with the innovator for oxynitrilases as organic catalysts. The innovator and our aldehyde technology found each other.

"We also make chiral derivatives of glyoxal and glyoxylic acid. Clariant is a major producer of C2 building blocks, including ketene. Glyoxal, glyoxylic acid, and monochloroacetic acid are all C2 compounds in different variations. Clariant builds chiral chemistry on the basis of its vast expertise in C2 chemistry.

"Going forward, we have installed a biocatalysis group, and we are working with a partner to commercialize what we believe is a breakthrough method for separating racemates and purifying chiral compounds."


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