57573-45-2Relevant academic research and scientific papers
Chemoenzymatic dynamic kinetic resolution of primary amines catalyzed by CAL-B at 38-40°c
Poulhes, Florent,Vanthuyne, Nicolas,Bertrand, Michele P.,Gastaldi, Stephane,Gil, Gerard
body text, p. 7281 - 7286 (2011/10/10)
The (R)-selective chemoenzymatic dynamic kinetic resolution of primary amines was performed at 38-40 °C in MTBE, in good to high yields and with high enantiomeric excesses. These reactions associating CAL-B to octanethiol as radical racemizing agent were carried out in the presence of methyl β-methoxy propanoate as acyl donor, under photochemical irradiation at 350 nm in glassware.
Discovery of a novel series of biphenyl benzoic acid derivatives as highly potent and selective human β3 adrenergic receptor agonists with good oral bioavailability. Part II
Imanishi, Masashi,Itou, Shinji,Washizuka, Kenichi,Hamashima, Hitoshi,Nakajima, Yutaka,Araki, Takanobu,Tomishima, Yasuyo,Sakurai, Minoru,Matsui, Shigeo,Imamura, Emiko,Ueshima, Koji,Yamamoto, Takao,Yamamoto, Nobuhiro,Ishikawa, Hirofumi,Nakano, Keiko,Unami, Naoko,Hamada, Kaori,Matsumura, Yasuhiro,Takamura, Fujiko,Hattori, Kouji
experimental part, p. 4002 - 4020 (2009/05/07)
The left-hand side (LHS) and central part of our first generation biphenyl (FGB) series was modified to improve in vitro and in vivo β3-AR potency without loss of oral bioavailability. First, in this study, we focused our efforts on replacement of the 3-chlorophenyl moiety in the LHS of FGB analogues with 3-pyridyl ring analogues to adjust the lipophilicity. Second, we investigated the replacement of the central part of this series and discovered that introduction of a methyl group into the α-position of the phenethylamine moiety greatly enhanced potency keeping good oral availability. Finally, the replacement of the two carbon linker of the central part with an ethoxy-based linker provided improved potency and PK profiles. As a result of these studies, several analogues (i.e., 9h, 9k, 91, 10g, 10m, 10p, 10r, 11b, and 11l) were identified that displayed an excellent balance of very higher human β3-AR potency compared to the FGB compounds, high selectivity, and good pharmacokinetic profiles. Furthermore, these several compounds showed high in vivo efficacy in an overactive bladder (OAB) model. These findings suggest that our selected second generation biphenyl (SGB) series compounds may be attractive new successful therapeutic candidates for the treatment of OAB.
Synthesis of Enantiopure Homoallylic Alcohols and Ethers by Diastereoselective Allylation of Aldehydes
Tietze, Lutz F.,Schiemann, Kai,Wegner, Christoph,Wulff, Christian
, p. 1164 - 1172 (2007/10/03)
Enantiopure homoallylic alcohols 5, which are important building blocks in organic synthesis, are obtained with an ee of greater than 99percent and a yield of 75-95percent by cleavage of the secondary homoallylic ethers 4 using sodium in liquid ammonia.The ethers 4 are formed with excellent diastereoselectivity and in 52-89percent yield by treatment of the aldehydes 1 with the trimethylsilyl ether of N-trifluoroacetylnorpseudoephedrine (2) in the presence of a catalytic amount of TMS triflate or TMS borontriflate, followed by addition of allylsilane 3.Nearly all achiral aliphatic aldehydes employed gave a diastereoselectivity of over 99:1.With the chiral aldehydes 24, the difference between matched and mismatched pairs was low; this reveals that there is strong reagent control.- Keywords: allylations; allylsilanes; double stereodifferentiation; ephedrine; homoallylic alcohols
