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A Novel, Green Synthesis of Deuterium Labeled Compounds
Author(s) -
Kadish Dora,
Kokel Anne,
Torok Marianna,
Torok Bela
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.607.7
Subject(s) - deuterium , chemistry , reactivity (psychology) , catalysis , hydrogen , tritium , molecule , hydrogen–deuterium exchange , organic synthesis , combinatorial chemistry , radiochemistry , nuclear chemistry , organic chemistry , medicine , physics , alternative medicine , pathology , quantum mechanics , nuclear physics
While deuterium (D) is barely different from its most abundant isotope hydrogen (H), the additional neutron makes a significant difference in the properties of deuterated compounds. While metabolic enzymes easily transform drug molecules to metabolites that the body can excrete, the introduction of deuterium to drugs appears to strengthen the resistance of drugs toward metabolism. The higher the stability, the longer the drug can work, which may result in lower dosage, therefore less side effects. In fact, the carbon‐deuterium bond is known to be six‐ten times stronger than its C‐H counterpart. There are several known methods for the introduction of deuterium to organic compounds; most methods, however, do not conform to the recent expectations and standards of sustainable synthesis. In order to develop an environmentally benign deuteration method we have turned our attention to the Al‐H 2 O system that is commonly applied for hydrogenation reactions. Replacing the H 2 O with its deuterated version D 2 O this hydrogen generating system can be turned to an easy and safe source of deuterium. The application of either the commercially available Ni‐Al alloy or Al only in conjunction with common hydrogenation catalysts, such as Pd or Pt, for the H‐D exchange of compounds with reactive C‐H bonds can be easily performed, while yielding no harmful byproducts. The low reactivity of the aluminum metal can be significantly enhanced by the application of ultrasonic irradiation. The H‐D exchange reaction can be carried out under relatively mild conditions; in more difficult cases the application of microwave irradiation yields the final products in a 1 h reaction. The success of the method was demonstrated by applying a broad variety of compounds from essential amino acids to actual drug compounds. By generating stronger bonds, the drugs would be able to remain active for an extended period of time, allowing the use of lower amounts, thus significantly improve the safety of their use.