350031-22-0Relevant academic research and scientific papers
Scalable Total Syntheses and Structure–Activity Relationships of Haouamines A, B, and Their Derivatives as Stable Formate Salts
Tsukamoto, Hirokazu,Nakamura, Saki,Tomida, Akito,Doi, Takayuki
supporting information, p. 12528 - 12532 (2020/09/09)
Haouamines A, B, and their derivatives were synthesized via Suzuki–Miyaura coupling and three key cyclization reactions as follows: the newly developed palladium(0)-catalyzed arylative cyclization of phenylalanine-derived alkyne–aldehydes with 2-bromoarylboronic acid (an “anti-Wacker”-type cyclization); BF3?OEt2-promoted Friedel–Crafts-type cyclization of symmetrical electron-rich aromatic rings adjacent to a tertiary allylic alcohol leading to the indeno-tetrahydropyridine skeleton; and (cyanomethyl)trimethylphosphonium iodide-mediated macrocyclization of amino alcohols to afford aza-paracyclophane precursors. The palladium-catalyzed reduction of mono- and di-triflate intermediates in the later stages enabled the alteration of both the position and number of hydroxyl groups on the C-ring. The instability of haouamine B was dramatically improved by salt formation with formic acid. An unambiguous evaluation of the cytotoxicity of the prepared haouamine derivative formates with and without hydroxyl groups at different positions on the C-ring indicated that the catechol structure in haouamine B produced weak cytotoxicity.
Asymmetric synthesis of 3-substituted cyclohexylamine derivatives from prochiral diketones via three biocatalytic steps
Siirola, Elina,Mutti, Francesco G.,Grischek, Barbara,Hoefler, Sebastian F.,Fabian, Walter M. F.,Grogan, Gideon,Kroutil, Wolfgang
supporting information, p. 1703 - 1708 (2013/07/19)
Prochiral bicyclic diketones were transformed to a single diastereomer of 3-substituted cyclohexylamine derivatives via three consecutive biocatalytic steps. The two chiral centres were set up by a C-C hydrolase (6-oxocamphor hydrolase) in the first step and by an ω-transaminase in the last step. The esterification of the intermediate keto acid was catalysed by a lipase in the second step if possible. For two substrates the C-C hydrolytic step as well as the esterification could be run simultaneously in a one-pot cascade in an organic solvent. In one example, the reaction mixture of the first two steps could be directly subjected to bio-amination in an organic solvent without the need to change the reaction medium. Depending on the choice of the ω-transaminase employed and the substrate the cis- as well as the trans-diastereomers could be obtained in optically pure forms. Copyright
An asymmetric enzyme-catalyzed retro-claisen reaction for the desymmetrization of cyclic β-diketones
Grogan, Gideon,Graf, Juergen,Jones, Aileen,Parsons, Simon,Turner, Nicholas J.,Flitsch, Sabine L.
, p. 1111 - 1114 (2007/10/03)
Unsymmetrical is beautiful: Enzymatic desymmetrization offers a mild route to chiral synthons with, in principles, 100% yield and absolute optical purity. The technique has been applied to bicyclic β-diketones for the first time, through a novel enzymatic retro-Claisen reaction, to yield chiral cyclic keto acids in up to 91% yield and 94% ee (see scheme, step a).
Asymmetric Michael addition of malonate anions to prochiral acceptors catalyzed by L-proline rubidium salt
Yamaguchi, Masahiko,Shiraishi, Tai,Hirama, Masahiro
, p. 3520 - 3530 (2007/10/03)
L-Proline rubidium salt catalyzes the asymmetric Michael addition of malonate anions to prochiral enones and enals. This method can be applied to a wide range of substrates to give adducts with a predictable absolute configuration: (S)-adducts from (E)-enones/enals and (R)-adducts from cyclic (Z)-enones. Both the secondary amine moiety and the carboxylate moiety are critical for the catalytic activity and asymmetric induction. Varying the countercation also affects the reaction course. High enantiomeric excesses were attained when di(tert-butyl) malonate was added to (E)-enones in the presence of CsF. The stereochemistry of the Michael reaction indicates that asymmetric induction takes place via enantioface discrimination involving the acceptor α-carbon atom rather than the β-carbon atom.
