- Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation
-
Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.
- Hill, Christopher K.,Hartwig, John F.
-
p. 1213 - 1221
(2017/11/28)
-
- Effect of metal ions on the stable adduct formation of 16α- hydroxyestrone with a primary amine via the Heyns rearrangement
-
16α-Hydroxyestrone (16α-OHE1), one of the major estrogen metabolites in humans that may plays a role in cell transformation, has been found to form stable adducts with nuclear proteins. The mechanism for the formation of a stable covalent adduct of 16α- OHE1 with protein has been postulated via the Heyns rearrangement after Schiff base formation. The Heyns rearrangement on the steroidal D-ring α-hydroxyimine was investigated using 17-(2- methoxyethylimino)estra-1,3,5(10)-triene-3,16α-diol as a model intermediate. Rates of the Heyns rearrangement and hydrolysis of the steroidal α- hydroxyimine were determined by a high-performance liquid chromatography (HPLC) simultaneously. The Heyns rearrangement was demonstrated to be optimum at pH 6.2 and the reaction rate at physiological pH, 7.3-7.5, was more than 90% of that at the optimum pH. On the other hand, modulator(s) to the reactions were also examined. According to our previous finding of the proton-mediated mechanism of the Heyns rearrangement, the effects of cationic metal ions on the reactions were examined with 29 metal chlorides. Five metal ions, Pt4+, Cu2+, Ni2+, Co2+, and Mn2+, suppressed the formation of Heyns product significantly while Fe2+, Y3+, Gd3+, and Er3+ slightly increased it. The suppression rate was synergistically enhanced by the combination of Pt4+ with Co2+, Cu2+, or Ni2+. These results suggest the five metal ions, Pt4+, Cu2+, Ni2+, Co2+, and Mn2+, reduce the formation of the Heyns product in vivo and, therefore, would be useful tools to clarify the implication of the stable adduct formation of 16α-OHE1 with protein.
- Miyairi, Shinichi,Maeda, Kaoru,Oe, Tomoyuki,Kato, Toyoaki,Naganuma, Akira
-
p. 252 - 258
(2007/10/03)
-
- Deoxygenation of steroidal ring-D 16,17-ketols with trimethylsilyl iodide
-
Reaction of various steroidal 16,17-ketols, 16α-hydroxy-17-ketones 1- 3, and 15, 16β-hydroxy-17-ketone 4, and 17β-hydroxy-16-ketones 5-7, and 17, along with methyl ethers of 16α- and 17β-ketols 1 and 5, with an excess of trimethylsilyl iodide (TMSI) or with HI in CHCl3, produced the deoxygenated products, a mixture of the corresponding 17- and 16-ketones, in low to quantitative yields, in which the 17-ketone was the major product in each ease. When the 16β-deuterated 16α-ketol 3 and the 17α-deuterated 17β- ketol 7 were reacted with TMSI for a brief period (15 min), the deuterium content at C-16β and C-17α of the recovered steroids 3 and 7 was reduced by 17 and 35%, respectively. The present results indicate that the deoxygenation proceeds not only through a direct iodination pathway producing α-iodoketone but also through other reaction pathways.
- Nagaoka, Masao,Nagasawa, Etsuko,Numazawa, Mitsuteru
-
p. 1857 - 1861
(2007/10/03)
-
- PREPARATION OF 16-SUBSTITUTED 3-HYDROXYESTRA-1,3,5(10)-TRIENE-17-ONE STARTING WITH THE BROMINATION OF ESTRONE ACETATE
-
The bromination of estrone acetate (Ia) leads to a mixture of acetates of 16α-bromo-16β-bromo-, and 16,16-dibromoestrone (IIa, IIIa, and IVa) in a ratio of 63:28:9.On treatment with an aqueous methanolic solution of potash, depending on the conditions, a mixture of (IIa) and (IIIa) gives 3,16α-dihydroxyestra-1,3,5(10)-trien-17-one (V) or 3,17β-dihydroxyestra-1,3,5(10)-trien-16-one (VI).When 5 g of (Ia) was brominated with 2.8 g of Br2 in chloroform and the products were chromatographed on silica gel, 0.36 g of (IVa), C20H22Br2O3, mp 165-166 deg C (from ether) 0.37 g of (IIIa), mp 169-170.5 deg C, 4.6 g of a mixture of (IIa) and (IIIa), 30 mg of (Ia) and 0.2 g of a mixture of 16α- and 16β-bromoestrones was obtained.The action of potash on a mixture of (IIa) and (IIIa) in aqueous MeOH at 20 deg C led to the epimerization of the (IIa) into (IIIa) and then the conversion of the latter into (V) with mp 203.5-206 deg C; diacetate with mp 172-173 deg C (acetone-ethanol).Similarly, but with heating (98 deg C, 3 h), a mixture of (IIa) and (IIIa) was converted into (VI), with mp 234-236 deg C.Characteristics of the IR and PMR spectra of the compounds obtained are given.
- Fedorova, O. I.,Morozova, L. S.,Alekseeva, L. M.,Grinenko, G. S.
-
p. 437 - 440
(2007/10/02)
-