126307-45-7Relevant articles and documents
Lewis Acid-Catalyzed Addition of Benzophenone Imine to Epoxides Enables the Selective Synthesis and Derivatization of Primary 1,2-Amino Alcohols
Leitch, David C.,Lim, John Jin
, p. 641 - 649 (2018/05/14)
Benzophenone imine was found to be an effective ammonia surrogate for the selective preparation of primary 1,2-amino alcohols from epoxides, including enantiopure epichlorohydrin, in the presence of catalytic Y(OTf)3. High-throughput screening of 48 Lewis acids quickly identified Y(OTf)3 as an effective mediator of the addition reaction under mild conditions. Following acidic hydrolysis, the primary amino alcohol salt is revealed and partitions into the aqueous solution, while the benzophenone byproduct is easily removed by simple extraction with ethyl acetate. These ammonium salts can be directly Boc-protected or further derivatized without isolation to form benzamides and sulfonamides under Schotten-Baumann-type conditions in up to 79% isolated yield over three steps. This methodology has been used to prepare key intermediates for the synthesis of PRMT5 inhibitors with high enantiopurity as well as numerous other amide and sulfonamide derivatives.
ESTRA-1,3,5(10),16-TETRAENE-3-CARBOXAMIDES FOR INHIBITION OF 17Β-HYDROXYSTEROID DEHYDROGENASE (AKR1 C3)
-
, (2016/02/18)
The invention relates to AKR1C3 inhibitors of formula (I) and to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of bleeding disorders and endometriosis.
Electrochemical Decarboxylation of L-Threonine and Oligopeptide Derivatives with Formation of N-Acyl-N,O-acetals: Preparation of Oligopeptides with Amide or Phosphonate C-Terminus
Seebach, Dieter,Charczuk, Roland,Gerber, Christian,Renaud, Philippe,Berner, Heinz,Schneider, Helmut
, p. 401 - 425 (2007/10/02)
Derivatives of α-amino acids with two stereogenic centers (cf.L-threonine) and di-, tri- and tetrapeptides are electrolyzed in MeOH or AcOH, with formation of N-acyl-N,O-acetals (1b - 15b, 20b), in an anodic oxidative substitution of the COOH by an OR group.The amine ends of the oligopeptides may be benzyloxycarbonyl(Z)- or (tert-butoxy)carbonyl(Boc)-protected.With unprotected dipeptides, an electrolytic decarboxylative cyclization to imidazolidinones (18c, 19c) may also occur (in H2O/NH4OAc).The electrolyses are carried out in simple flasks with cooling jackets ('undivided cell'), using constant current conditions and anodes of Pt or glassy C.The electrolyte is generated in situ by adding 10 - 20 mol-percent of a tertiary amine.Mild acidic hydrolysis of electrolysis products thus obtained may lead to amino-acid amides or peptide amides (10c, 11c, 12c, 17c) with one amino acid less than the starting material.The N,O-acetals from L-threonine and the oligopeptides also react with organometallic nucleophiles such as Grignard compounds (->21 - 26, 29), with formation of products in which the original COOH group has been replaced by alkyl or allyl (sometimes even with moderate stereoselectivity).By treatment of the peptide-derived (open-chain) N,O-acetals with trialkyl or triaryl phosphites/TiCl4, the RO group is replaced by a phosphodiester group in a (non-diastereoselective) Michaelis-Arbuzov-type reaction (1d, 1e, 2d - 9d, 5e).Thus, the two-step sequence of electrolysis and phosphonation converts an oligopeptide derivative to an analogue with a phosphonic-acid end group.The diastereoisomeric N-protected dimethyl and diethyl dipeptidephosphonates (also prepared from the corresponding diaryl esters by Ti(OR)4-mediated transesterification) could be separated by preparative HPLC (SiO2, Lichrosorb Si 60, 10 μm); the dextrorotatory isomers of 1d - 3d were assigned L,D-, the laevorotatory ones L,L-configuration by hydrolysis to and identification of the known amino and aminophosphonic acids.The results described demonstrate a new simple route leading, from a give oligopeptide, to pure peptide analogues of known configuration.