A library of isopulegol-based bi-, tri- and tetrafunctional chiral ligands has been developed from commercially available (−)-isopulegol and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. Michael addition of primary amines towards α-methylene-γ-butyrolactone, followed by reduction, was accomplished to provide aminodiols in highly stereoselective transformations. Stereoselective epoxidation of (+)-neoisopulegol, derived from natural (−)-isopulegol, and subsequent oxirane ring opening with primary amines afforded aminodiols. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. Hydroxylation of (+)-neoisopulegol resulted in diol, which was then transformed into aminotriols by aminolysis of its epoxides. Dihydroxylation of (+)-neoisopulegol or derivatives with OsO4/NMO gave neoisopulegol-based di-, tri- and tetraols in highly stereoselective reactions. The antimicrobial activity of aminodiol and aminotriol derivatives as well as di-, tri- and tetraols was also explored. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol and aminotriol systems.

A library of 1,2-aminoalcohol derivatives with a neoisopulegol-based octahydrobenzofuran core was developed and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The allylic chlorination of (+)-neoisopulegol, derived from natural (-)-isopulegol followed by cyclization, gave the key methyleneoctahydrobenzofuran intermediate. The stereoselective epoxidation of the key intermediate and subsequent oxirane ring opening with primary amines afforded the required 1,2-aminoalcohols. The ring closure of the secondary amine analogues with formaldehyde provided spiro-oxazolidine ring systems. The dihydroxylation of the methylenetetrahydrofuran moiety with OsO 4 /NMO (4-methylmorpholine N-oxide) resulted in the formation of a neoisopulegol-based diol in a highly stereoselective reaction. The antimicrobial activity of both the aminoalcohol derivatives and the diol was also explored. Molecules 2020, 25, 21 2 of 14 antimalarial [26-28], and antileishmanial [29] agents. The 1,2-aminoalcohol function is found in a broad range of β-adrenergic blockers that are used extensively in the management of cardiovascular disorders [30], including hypertension, angina pectoris and cardiac arrhythmias, and other disorders that are related to the sympathetic nervous system [31,32]. 1,2-aminoalcohols have also been demonstrated to be excellent chiral auxiliaries and chiral catalysts in asymmetric synthesis [33]. To achieve new, efficient, and commercially available chiral catalysts, natural chiral terpenes, such as α-pinene [34-38], β-pinene [34,39], (-)-3-carene [39,40], (-)-verbenone [41,42], (-)-fenchone [43,44], (+)-camphor [43,45,46], and (-)-menthone [47] have proven to be excellent sources for the synthesis of bifunctional chiral compounds and heterocycles.In the present work, we set out to create a compound library with a (+)-neoisopulegol-based octahydrobenzofuran core and 1,2-aminoalcohol moieties. The synthesis started from commercially available (-)-isopulegol and then utilizing the resulting 1,2-aminoalcohol derivatives as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde. Furthermore, the antimicrobial activities of the synthesized compounds were also tested on multiple bacterial and fungal strains. Results Synthesis of Key Intermediate 3Key intermediate (-)-3-methylenetetrahydrofuran 3 was prepared from commercially available (-)-isopulegol 1 by oxidizing its hydroxyl function, followed by the stereoselective reduction of the resulting carbonyl group, thus providing (+)-neoisopulegol 2 [48][49][50][51]. The allylic chlorination of (+)-neoisopulegol 2 was followed by the cyclization-produced (-)-methylenetetrahydrofuran 3 [52-55], which was transformed into (−)-methylenetetrahydrofuran 4 by allylic oxidation after applying the literature method [55,56] (Figure 1).

β-Galactosidases of Mucoromycota are rarely studied, although this group of filamentous fungi is an excellent source of many industrial enzymes. In this study, 99 isolates from the genera Lichtheimia, Mortierella, Mucor, Rhizomucor, Rhizopus and Umbelopsis, were screened for their β-galactosidase activity using a chromogenic agar approach. Ten isolates from the best producers were selected, and the activity was further investigated in submerged (SmF) and solid-state (SSF) fermentation systems containing lactose and/or wheat bran substrates as enzyme production inducers. Wheat bran proved to be efficient for the enzyme production under both SmF and SSF conditions, giving maximum specific activity yields from 32 to 12,064 U/mg protein and from 783 to 22,720 U/mg protein, respectively. Oligosaccharide synthesis tests revealed the suitability of crude β-galactosidases from Lichtheimia ramosa Szeged Microbiological Collection (SZMC) 11360 and Rhizomucor pusillus SZMC 11025 to catalyze transgalactosylation reactions. In addition, the crude enzyme extracts had transfructosylation activity, resulting in the formation of fructo-oligosaccharide molecules in a sucrose-containing environment. The maximal oligosaccharide concentration varied between 0.0158 and 2.236 g/L depending on the crude enzyme and the initial material. Some oligosaccharide-enriched mixtures supported the growth of probiotics, indicating the potential of the studied enzyme extracts in future prebiotic synthesis processes.

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