Key movers

30 May 2002 00:00  [Source: APC]

Nobel prize-winning chiral technology is revolutionising the drug industry. APC profiles the latest range of processes and technologies to be launched on the market

Chiral catalysis has moved to the front of the chemical news agenda, after the 2001 Nobel Prize for chemistry award went to Ryoji Noyori and WilliamKnowles for their work on chirally catalysed hydrogenation reactions, and BarrySharpless, for his work on chirally catalysed oxidation reactions.

The Nobel Prize recognised that chiral molecules are now key to the pharmaceutical industry: around half the drugs on the market and more than 80% in the pipeline are chiral molecules.

The technologies for production of chiral molecules in single enantiomer form are becoming the differentiating factors in the fine chemicals sector. Much investment has been made in the development and in-licensing of chiral technologies.

Avecia has a chiral technologies portfolio that has benefited from both internal development and in-licensing. Avecia's chemists have developed its proprietary catalytic asymmetric transfer hydrogenation (CATHy) catalysts and processes over the past five years. The process can be used to produce chiral alcohols and amines in high chemical and optical yield without using hydrogen.

CACHy technology licence

Avecia licensed in catalytic asymmetric cyanohydrin catalysis (CACHy) C-C bond forming technology, which was developed by Yuri Belokon of the Russian Academy of Sciences and Michael North of Kings College London. Avecia claims the process is an efficient route to producing chiral cyanohydrins in high chemical and optical yield.

Avecia's third synthetic process is catalytic asymmetric organozinc technology, which was developed by the company's own chemists. The process is an enantioselective and chemoselective method for chiral C-C bond formation, which enables convergent syntheses.

Avecia has also invested in chiral separation technology. Avecia will license and co-fund development of the molecular recognition approach to chiral separation developed by the Puragen division of IBC Advanced Technologies. IBC's molecular recognition technology is based on supramolecular chemistry. Macrocylic molecules, which interact with and selectively bind chemical groups, are covalently attached to polymer or silica beads. The beads are packed in a column, through which the racemic mixture is passed. One of the enantiomers is selectively bound to the functionalised surface, while the other passes through the column. The bound isomer can easily be stripped from the column by altering the conditions in the column.

At Informex,Avecia announced a collaboration with Synetix Chiral Technologies on the development of immobilised catalysts for pharmaceuticals manufacturing.

Recent collaborations

Synetix's deal withAvecia is the latest in a series of collaborations over the past year. Rhodia ChiRex and Synetix are collaborating to develop and manufacture immobilised catalysts for use in the manufacture of pharmaceutical intermediates and fine chemical compounds. Synetix has successfully immobilised Rhodia ChiRex's proprietary cobalt-SALEN catalyst, which is used in Rhodia ChiRex's Jacobsen Hydrolytic Kinetic Resolution Technology, licensed from Harvard in 1996. Synetix will now manufacture commercial quantities of the newly immobilised catalyst for Rhodia ChiRex.

Synetix plans to develop an improved synthetic route for the PhanePhos ligand, having recently licensed the phosphine-based ligand for enantioselective hydrogenation from its developers, Merck. Denis Geffroy, Synetix's commercial manager, says Synetix planned to develop a replicable, scalable and economic route to the ligand in order to produce kilogramme quantities.

Synetix will sub-license the ligand to third party fine chemical and pharmaceutical companies. It is working on a commercial project using the ligand with a commercial partner.

Once the improved synthetic route for PhanePhos is developed, Synetix plans to use the ligand in conjunction with its immobilisation technology. Geffroy says the ligand could be fixed to the inorganic support, either cationically through a metal centre or covalently through a linker molecule attached to the aromatic ring of the ligand.

Rhodia ChiRex has a range of chiral technologies, including the Jacobsen Hydrolytic Kinetic Resolution technology for synthesis of diols and epoxides; Jacobsen's Asymmetric Epoxidation technology for conversion of cis olefins to the corresponding epoxides; Sharpless' Asymmetric Dihydroxylation technology for the synthesis of chiral diols from olefins; Jacobsen's amino acid technology, which produces chiral amino acids and derivatives from aldehydes; asymmetric reduction technology from Seprachem, which uses an aminoindanol based oxaborazolidine catalyst to effect the reduction of a prochiral ketone to a chiral alcohol; and Jacobsen's Asymmetric Ring Opening technology for the conversion of meso epoxides to chiral azido alcohols which can be reduced to amino alcohols.

Last year,Dow gained a range of chiral technologies from Chirotech, following the purchase of Ascot. Chirotech has readily manipulated small-molecule catalysts for enantioselective transformations, which it says constitute an extremely versatile and economically advantageous method for the manufacture of a wide range of enantiomerically pure compounds. As well as continually developing its own catalysts, Chirotech has in-licensed several asymmetric catalytic technologies that are inherently amenable to large scale production.

Exclusive licence

Chirotech has the exclusive world wide licence for the chiral DuPHOS/BPE asymmetric hydrogenation ligands for use in the pharmaceutical, flavour and fragrance industries, the Trost palladium and molybdenum ligands for asymmetric allylic substitution.

Early last year,Chirotech announced that it had developed a catalyst for the asymmetric hydrogenation of ketones, which combined Merck's PhanePhos ligands with the bis-ruthenium diamine complex developed by Ryoji Noyori. The PhanePhos-ruthenium diamine complex reduces ketones to chiral alcohols.

ChiroTech also added HexaPHEMP to its toolbox of phosphine ligands for asymmetric catalysis last year. HexaPHEMP is a biaryl phosphine that can be applied to the asymmetric catalytic hydrogenation of imines when used in conjunction with Professor Ryoji Noyori's asymmetric ketone reduction technology. HexaPHEMP metal catalysts can also be used for hydrogenation of beta-keto esters, and other substrates for which alternative biaryl phosphine ligands are used.

For the latest chemical news, data and analysis that directly impacts your business sign up for a free trial to ICIS news - the breaking online news service for the global chemical industry.

Get the facts and analysis behind the headlines from our market leading weekly magazine: sign up to a free trial to ICIS Chemical Business.

Printer Friendly