Process Development of Chiral compounds

We strived to develop processes to produce various chiral compounds. Our efforts were especially directed to the technology development of “Asymmetric chemical catalyst”, “Bio catalyst”, “Optical resolution” and “Chiral pool”. By 1) Combining these technologies, 2) Ensuring costs and availability of starting materials and 3) Confirming the overall advantage of the process itself, we offer the optimum process to the customers.

	Technology

Asymmetric chemical catalyst

We have developed commercially viable reactions using effective chemical catalysts for asymmetric synthesis. One is a asymmetric phase transfer catalyst(Maruoka Catalyst®)effective to synthesize Unnatural Amino Acids invented by Prof. Maruoka(Kyoto Univ.) and ALB catalyst for asymmetric Michael reaction invented by Prof. Shibazaki(Tokyo Univ.)

Bio Catalyst

We have piled technologies to prepare targeted chiral compounds with the help of Bio catalyst(enzymes and microorganisms). Out of our own 8,500 strains, we choose best one for the aimed reaction and establish the process. The process will be further confirmed at larger scale at Nagase ChemteX so that the process can be commercially viable.


Examples of Bio catalysts developed by Nagase (PDF:276KB Japanese)

1. Heat resistant enzyme for hydrolysis : SNSM-87
2. Heat and organic solvents resistant protease : T-164
3. Hydrolysis enzyme for bulky molecule esters : KM109
4. Rabbit origin enzyme made from yeast : RLE
5. Immobilized catalyst Epoxidehydrolase
6. Preparation of lipophilic secondary alcohol using half ester of succinic acid
7. Bio reduction of optical selectivity in reverse to Hydride reduction
8. Hydroxide enzyme for Indole on optical selectivity

Optical resolution

We maintain our own library of commercially available optical resolving agents and we can search best one suitable for each purpose. Contained in our library is S-PBA, which is an effective resolving compound for various carbonic acids. We have also another compounds for amines resolution.

Chiral pool

We have developed rational production processes to obtain target chiral compounds from kinds of chiral carbon materials. Nagase has the function of sourcing such chiral raw materials at competitive and reasonable cost through our overseas net work. One example is converting a chiral alcohol to a fluorinated compound.

	Products

Unnatural Amino Acids

We can offer unnatural amino acids that are difficult to synthesize conventionally, otherwise by using Maruoka catalyst® rather simply, environmentally and friendly. We also develop commercial scale process as requested.

We have successfully produced not only D-type amino acid but ones with various substitutions. Chiral alcohols and amines are often derived from these amines. Depending on the target compound, we also make use of Bio catalyst, optical resolution, chiral pool, etc.

Unnatural amino acids synthesized by using Maruoka catalyst®(PDF:85KB Japanese)

1.α1-substituted amino acids from glycine derivatives by mono alkylation
2.α,α2-substituted amino acids from alanine derivatives by mono alkylation
3.α,α2-substituted amino acids from glycine derivatives by di alkylation
4.β- Methyl-α-amino acids from glycine derivatives by mono alkylation
5.β- Hydroxy-α-amino acids from glycine derivatives by Aldol reaction
6.γ-Amino acids by Michael addition reaction

Nagase's Library of Unnatural Amino Acids(PDF:591KB)

Nagase Provides Unnatural Amino Acids Using Maruoka Asymmetric Catalyst Technology(PDF:363KB)

Chiral carbonic acids

We can synthesize various chiral carbonic acids by using optical resolution and Bio catalysts. It is also possible to synthesize unique chiral carbonic acids with the help of Maruoka catalyst® and Shibazaki catalyst. β-Hydroxy carbonic acid can be made from chiral pool.

Chiral alcohols

We developed processes to produce kinds of chiral alcohols by using ester hydrolysis with the help of Bio catalysts, or asymmetric reduction of ketones. It is also possible to synthesize unique chiral alcohols by inducing chiral compounds using Maruoka catalyst® or Shibazaki Catalyst.

Chiral amines

We have established production processes of chiral amines mainly by optical resolution. We also possess the method of hydrolyzing nitriles to get chiral amines. Maruoka catalyst® also makes it possible to synthesize unique chiral amines through unnatural amino acids.

Drug discovery tools

We succeeded in developing evaluation systems utilizing human cells and microorganisms, which will enable pharmaceutical producing companies to conduct screenings of molecules at initial drug development stages. We also own libraries of microorganisms and compounds, that are available for customers as resources to produce new drugs.

Analysis and test services of imported drugs and intermediates

We conduct analysis and testing of drugs and intermediates imported by Nagase under GMP circumstances so that we can provide customers with products with reliable quality

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