68208-21-9Relevant articles and documents
Base-induced Sommelet–Hauser rearrangement of N-(α-(2-oxyethyl)branched)benzylic glycine ester-derived ammonium salts via a chelated intermediate
Baba, Souya,Hirano, Kazuki,Tayama, Eiji
supporting information, (2020/03/13)
The base-induced Sommelet–Hauser (S–H) rearrangement of N-(α-branched)benzylic glycine ester-derived ammonium salts 1 was investigated. When the α-branched substituent was a simple alkyl, such as a methyl or butyl, desired S–H rearrangement product 2 was obtained in low yield with formation of the [1,2] Stevens rearranged 4 and Hofmann eliminated products 5 and 6. However, when the α-branched substituent had a 2-oxy moiety, such as 2-acetoxyethyl or 2-benzoyloxyethyl, the yields of 2 were improved. These results could be explained by formation of chelated intermediate C that stabilizes the carbanionic ylide, and the subsequent initial dearomative [2,3] sigmatropic rearrangement would be accelerated. The existence of C was supported by mechanistic experiments. This enhancement effect is not very strong or effective; however, it will expand the synthetic usefulness of ammonium ylide rearrangements.
Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents
Adams, James,Anderson, Edward C.,Blackham, Emma E.,Chiu, Yin Wa Ryan,Clarke, Thomas,Eccles, Natasha,Gill, Luke A.,Haye, Joshua J.,Haywood, Harvey T.,Hoenig, Christian R.,Kausas, Marius,Le, Joelle,Russell, Hannah L.,Smedley, Christopher,Tipping, William J.,Tongue, Tom,Wood, Charlotte C.,Yeung, Jason,Rowedder, James E.,Fray, M. Jonathan,McInally, Thomas,Macdonald, Simon J. F.
supporting information, p. 1207 - 1212 (2015/04/27)
Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.
Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine
You, Pengyong,Qiu, Jian,Su, Erzheng,Wei, Dongzhi
, p. 557 - 565 (2013/03/13)
An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3- phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99 %). A carica papaya lipase catalysed resolution of N-protected β-phenylalanine esters has been developed. High enantioselectivity was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. After 50 % conversion, the products were separated and used as key chiral intermediates for the synthesis of (S)-dapoxetine with > 99 % ee. Copyright
