D-Ornithine Monohydrochloride CAS 16682-12-5

D-Ornithine monohydrochloride, as a non natural amino acid, has a wide range of applications in peptide drug synthesis, pharmaceutical intermediates, and pesticide synthesis.

The preparation of D-ornithine hydrochloride by arginine chemical enzyme method is achieved through the hydrolysis racemization reaction of arginine under alkaline conditions.

Through two steps of chemical racemization reaction and biological conversion, combined with biological enzyme conversion technology, L-arginine can be efficiently converted into a product.

This method has the advantages of simple operation and high yield. Provided strong technical support for the industrial production of this product.

Chemical racemization reaction:

C6H14N4O2 + NaOH + H2O → C5H12N2O2 + NaCl

C5H12N2O2 + HCl → C5H13ClN2O2

Biotransformation:

C5H12N2O2+Lysine Decarboxylase → C5H13ClN2O2+C4H12N2

C5H13ClN2O2 + HCl → C5H13ClN2O2

I. First Discovery of Ornithine (Late 19th Century)

In 1877, German chemist Jaffé first isolated a non-protein amino acid from the hydrolysate of urine of birds fed with benzoic acid, and named it Ornithine, laying the foundation for subsequent research. At that time, it was only known to exist in biological metabolites; its stereoisomeric configuration had not been distinguished, nor had its hydrochloride salt form been prepared.

II. Elucidation of L-Ornithine and Metabolic Pathways (Early to Mid-20th Century)

From 1904 to 1932, scientists gradually confirmed that natural ornithine predominantly exists in the L-configuration. It was found to participate in the urea cycle and act as a key intermediate for ammonia detoxification in the liver. Meanwhile, L-ornithine monohydrochloride became a commonly used form in biochemical research due to its excellent stability and easy crystallization. In contrast, D-ornithine received little attention for a long time owing to its extremely low natural abundance.

III. Resolution and Synthetic Breakthrough of D-Ornithine (Mid-to-Late 20th Century)

From 1950 to 1970, with the rise of research on amino acid stereochemistry, researchers used DL-ornithine as the raw material. High-purity D-ornithine was obtained for the first time via chemical resolution (e.g., fractional crystallization of tartrate salts) or enzymatic resolution (e.g., arginase hydrolysis), which was then reacted with hydrochloric acid to synthesize the product. After the 1980s, chemo-enzymatic synthesis (e.g., racemization of L-arginine combined with enzymatic resolution) greatly improved the yield and promoted large-scale production.

IV. Application Expansion and Commercialization (Late 20th Century to Present)

Since the 1990s, benefiting from its unique stereochemical configuration, the product has demonstrated great value in the fields of anti-tumor drug development, chiral ligand synthesis, biochemical probes and other research areas. It has gradually achieved commercial production and become an important intermediate in the pharmaceutical and fine chemical industries.