Le Tam Minh, Huynh Thu, Endre Gábor, Szekeres András, Fülöp Ferenc, Szakonyi Zsolt
Institute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary Excellence Centre Eötvös utca 6 H-6720 Szeged Hungary
Stereochemistry Research Group of the Hungarian Academy of Sciences Eötvös utca 6 H-6720 Szeged Hungary.
RSC Adv. 2020 Oct 19;10(63):38468-38477. doi: 10.1039/d0ra07739a. eCollection 2020 Oct 15.
A new family of isopulegol-based bi- and trifunctional chiral ligands was developed from commercially available (-)-isopulegol. Nucleophilic addition of primary amines towards (+)-α-methylene-γ-butyrolactone was accomplished, followed by reduction of the obtained β-aminolactones to provide aminodiols in highly stereoselective reactions. Epoxidation of (-)-isopulegol and subsequent oxirane ring opening with primary amines resulted in -substituted aminodiols. The regioselective ring closure of these aminodiols with formaldehyde was also investigated. Benzylation of isopulegol furnished -benzyl-protected isopulegol, which was transformed into aminoalcohols epoxidation and ring opening of the corresponding epoxides. First benzyl-protected isopulegol was subjected to hydroxylation and epoxidation, then aminolysis of the served oxiranes delivered aminodiols. On the other hand, (-)-isopulegol was oxidised to diol, which was again converted into both dibenzyl- and monobenzyl-protected diol derivatives. The products were transformed into aminoalcohols and aminodiols, respectively, by aminolysis of their epoxides. The ring opening of epoxides, derived from diols with primary amines was also performed producing aminotriols. Dihydroxylation of (-)-isopulegol or derivatives with OsO/NMO gave isopulegol-based di-, tri- and tetraols. The antimicrobial activity and antioxidant property, measuring DPPH˙ free radical scavenging activity of aminodiol and aminotriol derivatives as well as di-, tri- and tetraols were also explored. In addition, structure-activity relationships were examined from the aspects of substituent effects and stereochemistry on the aminodiol and aminotriol systems.
基于市售的（-）-异胡薄荷醇开发了一个新的基于异胡薄荷醇的双功能和三功能手性配体家族。伯胺对（+）-α-亚甲基-γ-丁内酯进行亲核加成，然后将所得的β-氨基内酯还原，以在高度立体选择性反应中提供氨基二醇。（-）-异胡薄荷醇的环氧化以及随后与伯胺的环氧乙烷开环反应生成了取代的氨基二醇。还研究了这些氨基二醇与甲醛的区域选择性闭环反应。异胡薄荷醇的苄基化得到苄基保护的异胡薄荷醇，其通过相应环氧化物的环氧化和开环反应转化为氨基醇。首先将苄基保护的异胡薄荷醇进行羟基化和环氧化，然后对所得的环氧乙烷进行氨解得到氨基二醇。另一方面，（-）-异胡薄荷醇被氧化为二醇，该二醇又被转化为二苄基保护的和单苄基保护的二醇衍生物。通过对其环氧化物进行氨解，产物分别转化为氨基醇和氨基二醇。由二醇与伯胺衍生的环氧化物的开环反应也进行了，生成了氨基三醇。用OsO₄/NMO对（-）-异胡薄荷醇或其衍生物进行二羟基化反应得到了基于异胡薄荷醇的二醇、三醇和四醇。还探索了氨基二醇和氨基三醇衍生物以及二醇、三醇和四醇的抗菌活性和抗氧化性能，通过测量DPPH˙自由基清除活性来评估。此外，还从取代基效应和立体化学方面研究了氨基二醇和氨基三醇体系的构效关系。
