Gaining Stereoselectivity in Asymmetric Synthesis

Researchers use inorganic catalysts as an alternative to biocatalysts in the selective conversion of sugars to produce chiral building blocks.
Feb 02, 2013
Volume 37, Issue 2

Chiral chemistry plays a significant role in the development of pharmaceutical intermediates and APIs, and as such, advances in asymmetric synthesis are of value to pharmaceutical companies. Researchers in academia and industry continue to develop new routes for achieving desired enantioselectivity.

Evaluating the opportunity

Patricia Van Arnum
The global market for chiral technology, inclusive of applications in pharmaceuticals, is expected to show moderate growth during the next five years. The global chiral technology market was worth nearly $5.3 billion in 2011, according to a recent analysis by BCC Research. This market is expected to increase at a compound annual growth rate (CAGR) of 6.5% from 2011 to 2016 and will approach $7.2 billion by the end of the forecast period. Chiral-synthesis products accounted for the majority of the chiral technology market in 2010, with an 80.% share (i.e., $3.9 billion in revenues). This market segment was estimated at $4.2 billion in 2011 and is expected to be $5.7 billion by 2016, a five-year CAGR of 6.4%, according to BCC. The chiral analysis market was valued at $785.7 million in 2010 and grew to $839.4 million in 2011. This market is projected to reach nearly $1.1 billion by 2016, a CAGR of 5.8% during the five-year period, according to BCC.

Generating sugar epimers

A review of recent literature reveals several interesting approaches in chiral chemistry. One approach involves the synthesis of rare sugars, which have potential in several important applications, including as chiral building blocks in natural-products synthesis. Current production methods, however, use costly and complex biochemical processes to transform easily found abundant sugars into these rare ones. To address this limitation, researchers at the Massachusetts Institute of Technology (MIT) have found a way to use inorganic catalysts in place of enzymes to generate sugar epimers in a simple and robust manner, according to a Oct. 10, 2012 MIT press release.

Typically, biochemical processes used to generate rare sugars from more abundant sugars involve three main classes of enzymes, two of which, isomerases and oxidoreductases, are active on a wide range of simple substrates, but which also can result in the formation of side products. For example, xylose isomerase converts glucose into fructose and simultaneously converts fructose into mannose. These processes have generated some commercially available rare sugars, but the complex nature of that biochemical process makes it costly, according to the MIT release. The third class of enzymes, epimerases, are potentially the most useful biocatalysts for the widespread production of rare sugars because they offer high specificity for products and are capable of selectively modifying sugars at multiple carbon positions. Like all biological catalysts, however, epimerases can be fragile because they require specific reaction conditions and can only act on previously functionalized sugars.

The MIT researchers reported using inorganic catalysts in place of the enzymes to generate sugar epimers, thereby offering an alternative to biocatalysts in the selective conversion of sugars (1). The catalytic system involves using a tin-substituted microporous silicate (Sn-Beta zeolite) combined with a borate salt. The MIT researchers found that Sn-Beta zeolite in the presence of sodium tetraborate catalyzed the selective epimerization of aldoses in aqueous media. The reaction proceeds by way of a 1,2 carbon-shift mechanism, whereby C–C bonds move within the molecule's backbone, according to the MIT release.

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