Apis Are Not the Only Game in Town

The pharmaceutical chemicals market is so broad that companies not aiming for high-profile, megabucks contract manufacturing of regulated products--active pharmaceutical ingredients (APIs) or advanced intermediates--can fill unique niches. FMC Lithium and Engelhard are two examples.

FMC Lithium is known for lithium-derived chemicals such as alkyllithiums, aryllithiums, lithium amides, and lithium alkoxides. Now, the company is hoping to grow by leveraging the products it already makes by using them in custom syntheses. With the message that it is more than just lithium, FMC Lithium now offers customized solutions to syntheses involving lithium reagents. The company has just patented a route to functionalized pyridines through lithium chemistry.

Functionalized pyridines are produced when the lithium of a lithiated pyridine is replaced by an electrophile, explains Gregory R. Hahn, global business director for organics. The lithiated pyridine is prepared by directed ortho-metalation, often with very high selectivity. Lithium attacks the position ortho to a directing group on the pyridine molecule. FMC Lithium is prepared to custom synthesize functionalized pyridines that are early intermediates in multistep syntheses of advanced intermediates or APIs in amounts ranging from grams to kilograms, Hahn says. Its facilities have been audited by several pharmaceutical companies, he adds.

On the other hand, Engelhard, a surface and materials science company, has been developing enabling technologies for the pharmaceutical and fine chemicals market. It recently launched three products aimed at making organic reaction processes more efficient: LigandNet, ScavNet, and DeLink. All products were developed in response to unmet needs of customers, says Bill Goodwin, market manager for process technologies.

LigandNet is a catalyst immobilization technology. The precious-metal precursor of a catalyst developed for homogeneous catalysis is tethered through a polymeric support to a substrate before it is transformed to the required catalyst. According to Goodwin, the immobilized catalysts prepared with LigandNet have activity and selectivity similar to the untethered versions. Other immobilizing methods usually lead to less activity and/or less selectivity, he adds.

Immobilizing makes it easy to separate the spent catalyst and to recover the precious metal for reuse. Goodwin says an asymmetric rhodium catalyst for chiral hydrogenation has been recovered and reused for up to three times without loss of activity or enantioselectivity.

ScavNet is a scavenging agent that removes homogeneous catalysts from organic reaction streams. Goodwin will not say what the agent is made of. The agent removes palladium, platinum, rhodium, and ruthenium as either cationic or neutral complexes. It grabs the last traces of metals from products sensitive to metal contamination and from solvents. The recovered metal, as well as treated solvents, can then be recycled. The technology will not only simplify purification but also greatly reduce metal contamination of products, Goodwin says.

DeLink is a palladium-on-carbon catalyst for removing protecting groups commonly used in organic synthesis, including those used in preparing peptides. Goodwin says the use conditions can be tailored so that the catalyst will attack only specific groups and leave alone vulnerable sites in the molecule, for example, centers of chirality.

Engelhard will not go into API manufacturing, Goodwin says. The company's strength is in providing tools and technical solutions related to catalytic and complementary technologies, he explains. The company is sticking with what it knows best.