Synthesis of chiral derivatives of hydroxyalkylamides

New and innovative aspects

Chiral organic compounds with hydroxyl groups are important synthetic precursors of amino acids, alkaloids, carbohydrates, and other chiral compounds with possible biological and / or pharmacological activity. That is why one of the main challenges of current organic chemistry is the search for new efficient and clean synthesis procedures that allow access to chiral compounds. The novel procedure described by the UBU researchers makes it possible to obtain a new family of derivatives of (6-hydroxyphenyl)-N,N-diethyl-3-hydroxyalkylamides, which are not described in the literature and which are obtained as a single diastereoisomer. The pharmacological relevance of both chiral organic compounds and epoxides is demonstrated by the fact that they are found or precursors of numerous biologically active compounds or natural products.

Main advantages of its use

• The process that makes it possible to obtain a new family of derivatives of (6-hydroxyphenyl)-N,N-diethyl-3-hydroxyalkylamides is novel.
• The compounds are not described in the literature and are obtained as a single diastereoisomer.
• The process can also be carried out using chiral epoxides, thus making it possible to obtain the final products in an enantiospecific way.

Specifications

The described procedure allows the synthesis of new compounds derived from (6-hydroxyphenyl)-N,N-diethyl-3-hydroxyalkylamides from O-aryl N,N-diethylcarbamates as starting substrates, being able to present groups of different chemical nature on the aromatic ring, such as halogens, methoxy groups, or unsubstituted. Likewise, the use of sec-butyllithium or lithium diisopropylamide is required, in tetrahydrofuran, at –78 ºC, atmospheric pressure and in an inert nitrogen gas atmosphere, for the ortho-lithiation reaction of the starting carbamates. The subsequent addition of lithium 2,2,6,6-tetramethylpiperidide and the addition of a terminal epoxide, which can be alkyl or with a functional group, both racemic and enantiomerically pure, gives rise to the homologous regrouping of Snieckus-Fries 1,4 -O → C of the carbamoyl group by the evolution of the reaction at room temperature for 3 hours.

Applications

The potential application of the described procedure is the synthesis of chiral aromatic organic compounds that contain alcohol groups in their structure, as well as halogens and other functional groups, for which they are postulated as highly versatile synthetic intermediates with great applicability in the pharmaceutical, agrochemical, industry. chemistry, etc.

Intellectual property status

Protected by patent P202130635

Current development status

Laboratory tested procedure.

Desired business relationship

Commercial Agreement, License Agreement, Technical Cooperation: further development; Technical Cooperation: testing new applications; Technical Cooperation: adaptation to specific needs.