Effective chiral pool synthesis of both enantiomers of the TRPML inhibitor trans-ML-SI3

Kriegler, Katharina; Leser, Charlotte; Mayer, Peter and Bracher, Franz (2021): Effective chiral pool synthesis of both enantiomers of the TRPML inhibitor trans-ML-SI3. In: Archiv der Pharmazie, Vol. 355, No. 2, e2100362

Abstract

Two independent chiral pool syntheses of both enantiomers of the TRPML inhibitor, trans-ML-SI3, were developed, starting from commercially available (1S,2R)- and (1R,2S)-configured cis-2-aminocyclohexanols. Both routes lead to the target compounds in excellent enantiomeric purity and good overall yields. For the most attractive (-)-trans-enantiomer, the R,R-configuration was identified by these unambiguous syntheses, and the results were confirmed by single-crystal X-ray structure analysis. These effective synthetic approaches further allow flexible variation of prominent residues in ML-SI3 for future in-depth analysis of structure-activity relationships as both the piperazine and the N-sulfonyl residues are introduced into the molecule at late stages of the synthesis.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0365-6233
• Language: English