MCA by-product route & limitations
In Asia in particular, many smallvolume monochloroacetic acid( MCA) manufacturers have identified process-related by-product DCA as a potential source for oligonucleotide applications. As more MCA manufacturers modify their MCA processes to improve process efficiency, the formation of DCA is no longer observed as a by-product.
As a result, the long-term availability of this source of DCA remains uncertain. DCA can be obtained via the MCA route from the residue generated during MCA production. In addition to numerous impurities, this residue typically contains significant amounts of DCA, together with trichloroacetic acid( TCA).
Owing to the similar physicochemical properties of DCA and TCA, their direct separation is
challenging. A commonly applied purification strategy involves converting chlorinated acetic acids such as DCA and TCA into their corresponding esters, followed by separation of the ester derivatives. Subsequent saponification of the isolated DCA ester regenerates free dichloroacetic acid.
However, this process can lead to the formation of glyoxylic acid as an undesired by-product. Glyoxylic acid is particularly problematic in oligonucleotide synthesis, as it can react with the growing oligonucleotide chain, significantly reducing yield and purity.
To improve DCA quality from this route, additional purification steps are required. One approach involves the use of glyoxylic acid scavengers such as cysteine, which selectively react with glyoxylic acid to form species that can be removed by a further manufacturing step. 3
Purpose-built route
An efficient and scalable route to high-purity DCA therefore requires a purpose-designed production technology based on tightly
% of crude product
3.5 3
2.5 2
1.5 1
0.5 0
Figure 2- LC / MS analyses of distribution of synthesis-related substances
DeTrityl Ultrapure Asian DCA Grade 1 Asian DCA Grade 2
N-1 N-2
N-3 N-4
N-5 N-6
N-7 N-8
N-9 N-10
N-11 N-12
N-13
N-14 N-15 Depurin …
22 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981