5390-04-5Relevant articles and documents
METHOD FOR PRODUCING 4-PENTYN-1-OL
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Paragraph 0038; 0039; 0040; 0041; 0042; 0043; 0044, (2019/09/20)
PROBLEM TO BE SOLVED: To provide a production method that can synthesize 4-pentyn-1-ol, which is useful as a synthetic raw material of agrochemicals or pharmaceuticals, without using any special reaction facility, in high yields, and in large quantity. SOLUTION: A method for producing 4-pentyn-1-ol includes causing the reaction between 2-chloromethyltetrahydrofuran and butyllithium to occur in an ether solvent excluding tetrahydrofuran. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
Asymmetric Synthesis of Functionalized trans-Cyclopropoxy Building Block for Grazoprevir
Xu, Feng,Zhong, Yong-Li,Li, Hongming,Qi, Ji,Desmond, Richard,Song, Zhiguo J.,Park, Jeonghan,Wang, Tao,Truppo, Matthew,Humphrey, Guy R.,Ruck, Rebecca T.
supporting information, p. 5880 - 5883 (2017/11/10)
A practical and asymmetric synthesis of a functionalized trans-cyclopropoxy building block for the preparation of the HCV NS3/4a protease inhibitor grazoprevir is reported. Intramolecular SN2 displacement-ring closure, followed by a Baeyer-Villiger oxidation, yields the desired trans-cyclopropanol with full control of diastereoselectivity. A terminal alkyne is then effectively installed using LiNH(CH2)2NEt2. Starting from (S)-epichlorohydrin, the cyclopropoxy building block is prepared in 51% overall yield with >99.8% optical purity without isolation of any intermediates.
Enzyme kinetics and inhibition of histone acetyltransferase KAT8
Wapenaar, Hannah,Van Der Wouden, Petra E.,Groves, Matthew R.,Rotili, Dante,Mai, Antonello,Dekker, Frank J.
, p. 289 - 296 (2015/11/09)
Lysine acetyltransferase 8 (KAT8) is a histone acetyltransferase (HAT) responsible for acetylating lysine 16 on histone H4 (H4K16) and plays a role in cell cycle progression as well as acetylation of the tumor suppressor protein p53. Further studies on its biological function and drug discovery initiatives will benefit from the development of small molecule inhibitors for this enzyme. As a first step towards this aim we investigated the enzyme kinetics of this bi-substrate enzyme. The kinetic experiments indicate a ping-pong mechanism in which the enzyme binds Ac-CoA first, followed by binding of the histone substrate. This mechanism is supported by affinity measurements of both substrates using isothermal titration calorimetry (ITC). Using this information, the KAT8 inhibition of a focused compound collection around the non-selective HAT inhibitor anacardic acid has been investigated. Kinetic studies with anacardic acid were performed, based on which a model for the catalytic activity of KAT8 and the inhibitory action of anacardic acid (AA) was proposed. This enabled the calculation of the inhibition constant Ki of anacardic acid derivatives using an adaptation of the Cheng-Prusoff equation. The results described in this study give insight into the catalytic mechanism of KAT8 and present the first well-characterized small-molecule inhibitors for this HAT.