Stereoselective synthesis and application of isopulegol-based bi- and trifunctional chiral compounds

Abstract

A new family of isopulegol-based bi- and trifunctional chiral ligands such as triols, tetrols, aminodiols and aminotriols was developed from commercially available (−)-isopulegol with antibacterial, antifungal and antioxidant activities.

Novel (+)-Neoisopulegol-Based O-Benzyl Derivatives as Antimicrobial Agents

“…Our previous work demonstrated that the O -benzyloxy group on the cyclohexyl ring is much more effective to induce antimicrobial activity. Therefore, to explore the role of the configuration of the O -benzyloxy group, some (−)-isopulegol-based O -benzyl derivatives were also prepared under optimized condition and using literature information [ 68 ] ( Scheme 5 ).…”

“…Debenzylation of 4b provided 44 in a moderate yield whereas exposure of 44 to NaOH furnished 45 with the retention of stereochemistry [ 86 ]. The absolute configuration of O -benzyl derivatives 19a and 25a was determined by debenzylation together with reduction via hydrogenolysis over Pd/C [ 87 , 88 ] to provide triol 45 with stereochemical retention [ 68 ]. The stereochemical structure of epoxide 44 is well-known in the literature [ 72 ]; therefore, the absolute configuration of O -benzyl derivatives could also be determined ( Scheme 6 ).…”

“…Since several O -benzyl derivatives exerted antimicrobial activities on various microorganisms [ 68 ], antimicrobial activities of the prepared O -benzyl analogues were also explored against two yeasts as well as two Gram-positive and two Gram-negative bacteria ( Table 1 , only the best results are shown). Furthermore, the minimal inhibitory concentrations (MIC) of the compounds showed significantly high level (>80%) antimicrobial activity and their MIC values were determined against the test microorganism, where the high inhibition activity was detected ( Table 1 , in brackets).…”

“…(+)-Neoisopulegol ( 2 ) ( = +28.7, c = 17.2, CHCl 3 ) and its enatimomer (−)- 2 ( = −22.2, c = 2.0, CHCl 3 ) were synthesized from (−)- 1 and its isomer (+)- 1 following a reported procedure, respectively [ 71 ]. Diol 17 , epoxide 44 [ 72 ] as well as compounds 29 , 33, and 37a – b [ 68 ] were prepared according to literature procedures. All spectroscopic data were similar to those described therein.…”

“…The increasing number of multidrug-resistant pathogen infections has led to the discovery of new antimicrobial drugs with activity against resistant clinical isolates [ 67 ]. In our long-term program toward the synthesis of new antimicrobial agents, we demonstrated that (−)-isopulegol-based O- benzyl aminotriol and aminodiol derivatives exert marked antimicrobial effectiveness [ 68 ]. Therefore, the present study reports the synthesis of a series of novel (+)-neoisopulegol-based O -benzyl derivatives of aminodiols and aminotriols with nitrogen atoms usually incorporated in an imidazole or triazole ring system possessing activity against various bacteria and yeast strains.…”