- Preparation method of optically pure 1, 1'-spirobiindane-6, 6'-diol derivative
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The invention discloses a preparation method of an optically pure 1, 1'-spirobiindane-6, 6'-diol derivative. The derivative is shown in the formula I. The optically pure 1, 1'-spirobiindane-6, 6'-diolderivative is prepared from optically pure N-benzylcinchonidinium chloride as an inclusion main body and a racemic 1, 1'-spirobiindane-6, 6'-diol derivative as a guest through an inclusion and resolution method. The novel method can acquire the 1, 1'-spirobiindane-6, 6'-diol derivative with high optical purity and chemical purity and acquire two structures in a high yield, has simple separation and purification processes, realizes recovery and recycling of a lot of a resolving agent, is simple and efficient, realizes a low cost and is suitable for industrial promotion. The optically pure 1, 1'-spirobiindane-6, 6'-diol derivative is a key raw material for the preparation of chiral spiro ligands or catalysts.
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Paragraph 0020-0022
(2019/03/17)
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- Bioactive indanes: Proof of concept study for enantioselective synthetic routes to ph46a, a new potential anti-inflammatory agent
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PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer catalysis, providing a key intermediate ketone (S)-4. The parent alkaloids required for the synthesis of PH46A, quinine or cinchonidine, have also been identified. Promising enantiomeric excesses of up to 50% have been achieved to date, and the use of an alternative substrate, unsaturated ketone 9, has also opened up further avenues for optimisation in future studies. The second part of the study involved preliminary screening the effects of a panel of hydrolase enzymes on (rac)-4 in order to identify a potential chemo-enzymatic route to optimise the introduction of chirality into PH46A at early stage of the synthesis. The hydrolase module has also yielded positive results; enzyme AH-46 with MtBE providing a selectivity factor of 8.4 with enantiomeric excess of 77%. Overall, positive results were obtained in this proof of concept study described herein. It is believed that conditions of both chiral PTC alkylation and biocatalytic hydrolysis could be optimised to further enhance the selectivity and improve the overall yield. This work is currently ongoing.
- Zhang, Tao,Scalabrino, Gaia,Frankish, Neil,Sheridan, Helen
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- Perfectly green organocatalysis: Quaternary ammonium base triggered cyanosilylation of aldehydes
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Quaternary ammonium bases, such as aqueous (CH3)4NOH, were found to be an extraordinarily efficient catalyst for cyanosilylation of aldehydes. The addition reaction of trimethylsilyl cyanide (TMSCN) to equivalent aldehydes could proceed smoothly with turnover frequency (TOF) up to 3000000 h-1 and in near 100% yield under solvent-free conditions. These organic catalysts also tolerated various aldehydes including aromatic, aliphatic and α,β-unsaturated aldehydes. This process perfectly conforms to the features of green chemistry: no waste regarding side-products and unconverted reactants, solvent-free, excellent catalytic activity, and no requirement for separation.
- Wen, Yeqian,Liang, Mengwei,Wang, Yiming,Ren, Weimin,Lue, Xiaobing
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p. 2109 - 2114
(2012/11/07)
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- Practical method and novel mechanism for optical resolution of BINOL by molecular complexation with N-benzylcinchoninium chloride
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A highly efficient and practical resolution of racemic 1,1'-bi-2- naphthol (BINOL) has been achieved through molecular complexation with N- benzylcinchoninium chloride, which can be readily prepared in 85% yield using an improved procedure through the reaction of cinchonine with benzyl chloride in dimethylformamide (DMF). It is found that the absolute configuration of BINOL included in the molecular crystals is R, which is the same as in the case of using N-benzylcinchonidinium chloride. This result is discussed in terms of molecular recognition in the solid state. X-Ray structural analysis of molecular crystal formed between (R)-BINOL and N-benzylcinchoninium chloride indicates that the additive effect of the chiral features of the host, the interaction pattern between the functional groups of the host and guest, and the complementary molecular packing in the crystal lattice dominates the stereochemistry of the guest in the molecular crystal. (C) 2000 Elsevier Science Ltd.
- Wang, Yang,Sun, Jie,Ding, Kuiling
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p. 4447 - 4451
(2007/10/03)
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