530-91-6Relevant articles and documents
A mechanistic study of the dihydroflavin reductive cleavage of the dihydroflavin-tetrahydronaphthalene epoxide adducts
Lee,Fisher
, p. 163 - 175 (2000)
Dihydroflavins are facile reducing agents and potent nucleophiles. The dihydroflavin nucleophilic reactivity, as measured by the rate of covalent flavin adduct formation with tetrahydronaphthalene epoxides, is comparable to that of the thiolate anion (Y. T. Lee and J. F. Fisher (1993) J. Org. Chem. 58, 3712). In these reactions there appears subsequent to the nucleophilic cleavage of the epoxide by the dihydroflavin the product corresponding to formal hydride reduction product (at the benzylic carbon) of these epoxides. Thus the reaction of (±)-1a,2,3,7b-tetrahydro-(1aα,2α,3β,7bα)-naphth[1,2-b]oxiren e-2,3-diol (1), (±)-1a,2,3,7b-tetrahydro-(1aα,2β,3α,7bα)-naphth[1,2-b]oxiren e-2,3-diol (2), and (±)-1a,2,3,7b-tetrahydro-(1aα,7bα)-naphth[1,2-b]oxirene (3) in 9:1 (v/v) aqueous Tris buffer-dioxane, at both acidic and neutral pH, with FMNH2 and 1,5-dihydrolumiflavin (LFH2) gave (following covalent flavin-epoxide adduct formation) the products having a methylene group at the benzylic position. The reduction product yield was proportional to the yield of the N(5) flavin-epoxide adduct intermediate, and the rate of the reaction was proportional to the dihydroflavin concentration. These observations are consistent with these reduction products resulting from bimolecular reaction between the dihydroflavin-epoxide adduct and a second molecule of dihydroflavin. (C) 2000 Academic Press.
Access to both enantiomers of substituted 2-tetralol analogs by a highly enantioselective reductase
Koesoema, Afifa Ayu,Matsuda, Tomoko,Standley, Daron M.,T. sriwong, Kotchakorn,Tamura, Mayumi
supporting information, (2020/02/11)
Both (S) and (R) forms of enantiomerically pure 2-tetralols, and their substituted analogs, are fundamental pharmaceutical intermediates. Here, we utilized the wild type and an engineered form of a highly enantioselective acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to produce (S)- and (R)-2-tetralols, and their substituted analogs. All mutations targeted residue Trp288, which has been shown to restrict substrate binding, but not play a direct role in catalysis. The wild type produced (S)-alcohols with excellent enantioselectivity, while the engineered forms produced either (S)- or (R)- alcohols, depending on the substituent on the aromatic ring of the substrate, indicating that enantioselectivity can be rationally controlled. As a result, we were able to produce 6-hydroxy-2-tetralol, a potential antifungal drug intermediate, with 98% ee (S) and 81% ee (R) by wild type and Trp288Ser GcAPRD, respectively. To our knowledge, this is the first report of generating chiral 6-hydroxy-2-tetralol by rational enzyme design.
Method for synthesizing tetrahydronaphthalene-2-alcohol derivative compound
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Paragraph 0026; 0032, (2020/07/21)
The invention relates to the technical field of compound preparation, and discloses a method for synthesizing a tetrahydronaphthalene-2-alcohol derivative compound, which comprises the following steps: (1) mixing a compound I with a palladium catalyst, an oxidant and a solvent, and carrying out sealed stirring reaction at 70-130 DEG C for 1-24 hours; carrying out post-treatment on the mixed solution obtained in the step (1) to obtain an intermediate product II; mixing the intermediate product II with a catalyst, acetonitrile and water, replacing air with nitrogen, and carrying out closed stirring reaction at 85-95 DEG C for 1-24 hours; and carrying out post-treatment on the mixed solution obtained in the step (3) to obtain a final product III, namely, the tetrahydronaphthalene-2-alcohol derivative compound. According to the method, intramolecular C (sp3)-H arylation is directly carried out through cross dehydrogenation coupling between inert C (sp3)-H and C (sp2)-H bonds to synthesizea benzopyran-3-alcohol derivative compound, the route is simple, the yield is high, the universality is good, the reaction condition is mild, and the selectivity is high.
