19013-37-7Relevant articles and documents
A Convenient Method for the Preparation of 3-Substituted Glutarate Diesters
Leotta, Gus J.,Overman, Larry E.,Welmaker, Gregory S.
, p. 1946 (1994)
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Toward aplyronine payloads for antibody-drug conjugates: Total synthesis of aplyronines A and D
An?i?ek, Nika,Williams, Simon,Housden, Michael P.,Paterson, Ian
supporting information, p. 1343 - 1350 (2018/03/06)
The aplyronines are a family of antimitotic marine macrolides that disrupt cytoskeletal dynamics by dual targeting of both actin and tubulin. Given their picomolar cytotoxicity profile and unprecedented mode of action, the aplyronines represent an excellent candidate as a novel payload for the development of next-generation antibody-drug conjugates (ADCs) for cancer chemotherapy. Enabled by an improved second-generation synthesis of the macrolactone core 5, we have achieved the first total synthesis of the most potent congener aplyronine D together with a highly stereocontrolled synthesis of aplyronine A. To facilitate step economy, an adventurous site-selective esterification of the C7 hydroxyl group was performed to install the N,N,O-trimethylserine pharmacophore to directly afford aplyronines A and D. Toward the assembly of ADCs incorporating an aplyronine warhead, the C29-ester derivative 4 featuring an Fmoc-amino substituted linker attached to the actin-binding tail region was also prepared by adapting this flexible endgame.
Preparation method of high-purity and high-yield monomethyl 3-methylglutarate
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Paragraph 0032; 0043-0045; 0054; 0055; 0065; 0066, (2018/09/08)
The invention relates to a preparation method of high-purity and high-yield monomethyl 3-methylglutarate, and belongs to the field of organic synthesis. The preparation method comprises the followingsteps of (1) esterification reaction: performing esterification reaction on beta-methylglutaric acid and methyl alcohol to obtain beta-dimethyl methylglutarate; (2) alkaline hydrolysis reaction: adding a barium hydroxide methyl alcohol solution into the obtained beta-dimethyl methylglutarate to generate barium salt of the monomethyl 3-methylglutarate; (3) finished product preparation: performing hydrochloric acid acidification, diethyl ether extraction and rectification and purification on the barium salt of the monomethyl 3-methylglutarate to obtain the monomethyl 3-methylglutarate. The prepared monomethyl 3-methylglutarate has the advantages of high yield, high purity and high mono-esterification selectivity. The preparation method is scientific and reasonable; simplicity is realized; the implementation is easy; the method is suitable for industrial mass production.
Two potent OXE-R antagonists: Assignment of stereochemistry
Patel, Pranav,Reddy, Chintam Nagendra,Gore, Vivek,Chourey, Shishir,Ye, Qiuji,Ouedraogo, Yannick P.,Gravel, Sylvie,Powell, William S.,Rokach, Joshua
supporting information, p. 815 - 819 (2014/08/05)
5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is formed by the oxidation of 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), which is a major metabolite of enzymatic oxidation of arachidonic acid (AA). 5-Oxo-ETE is the most potent lipid chemoattractant for human eosinophils. Its actions are mediated by the selective OXE receptor, which is therefore an attractive target in eosinophilic diseases such as allergic rhinitis and asthma. Recently, we have reported two excellent OXE receptor antagonists that have IC50 values at low nanomolar concentrations. Each of these antagonists has a chiral center, and the isolation of the individual enantiomers by chiral high-performance liquid chromatography (HPLC) revealed that in each case one enantiomer is over 300 times more potent than the other. To unambiguously assign the stereochemistry of these enantiomers and to provide access to larger amounts of the active compounds for biological testing, we report here their total synthesis.
