Calcium Pantothenate. Part 3. Process for the Biologically Active Enantiomer of the Same via Selective Crystallization and Racemization

Abstract

Optically pure calcium (R)-pantothenate has been obtained from the racemic compound via direct fractional crystallization of the single enantiomer. Efficient racemization of the biologically inactive calcium (S)-pantothenate without its decomposition to pantolactone has been developed, resulting in a simple, complete, and efficient technology. The results elaborated in the laboratory have been then successfully applied in the industrial scale process.

Processes To Separate Enantiomers

“…Also very recently, the advantages of preferential crystallization were proven for resolving racemic calcium pantothenate (with the (R)-enantiomer an important commercial precursor of vitamin B 5 ) and an industrially required resolving agent, both in lab and technical scale (35 L and 35 L) reaching high yields. [96,97] Detailed information on preferential crystallization can be found in several overview articles [e.g. 94,98] and book contributions.…”

Stereoselective Crystallization as a Basis for Single‐Enantiomer Drug Production

“…Apparently, methyldopa 35 should be considered as the first example of this kind, because its pure ( S )‐enantiomer has been produced industrially via direct resolution of the racemic product . Spontaneous resolution is a property exhibited by albuterol sulfate 36 and calcium pantothenate 37 .…”

Autorenregister / Stichwortregister

“…Darin werden insbesondere die Anwendung von Fließbettkristallisatoren und die kontinuierliche In‐situ‐Generierung von Impfkristallen zur Aufrechterhaltung des Prozessregimes hervorgehoben. Ebenfalls erst kürzlich konnte der erfolgreiche Einsatz der Bevorzugten Kristallisation für die Spaltung von racemischem Calciumpantothenat (dessen ( R )‐Enantiomer eine bedeutende kommerzielle Vorstufe von Vitamin B 5 ist) und eines industriell wichtigen Trennreagens gezeigt werden, wobei für beide sowohl im Labor‐ als auch im technischen (3000 L und 35 L) Maßstab hohe Ausbeuten erreicht wurden 96. 97…”