88481-75-8Relevant articles and documents
Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
supporting information, (2021/04/07)
Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates
Eno, Meredith S.,Lu, Alexander,Morken, James P.
, p. 7824 - 7827 (2016/07/11)
Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate.
Fluorinated Pseudopeptide Analogues of the Neuropeptide 26RFa: Synthesis, Biological, and Structural Studies
Pierry, Camille,Couve-Bonnaire, Samuel,Guilhaudis, Laure,Neveu, Cindy,Marotte, Amelie,Lefranc, Benjamin,Cahard, Dominique,Segalas-Milazzo, Isabelle,Leprince, Jerome,Pannecoucke, Xavier
, p. 1620 - 1633 (2013/09/23)
A series of four fluorinated dipeptide analogues each containing a fluoro-olefin moiety as peptide bond surrogate has been designed and synthesized. These motifs have been successfully introduced into the bioactive C-terminal heptapeptide of the neuropeptide 26RFa by conventional SPPS. We then evaluated the ability of the generated pseudopeptides to increase [Ca2+]i in GPR103-transfected cells. For these fluorinated analogues, greater stability in human serum was observed. Their conformations were also investigated, leading to the valuable identification of differences depending on the position of the fluoro-olefin moiety in the sequence.
Synthesis of sulfur-containing olefinic peptide mimetic farnesyl transferase inhibitors using the Nozaki-Hiyama-Kishi reaction and cuprate S(N)2' displacements
Yang, Hu,Sheng, Xiaoning C.,Harrington, Edmund M.,Ackermann, Karen,Garcia, Ana Maria,Lewis, Michael D.
, p. 242 - 251 (2007/10/03)
Syntheses of the potent sulfur-containing tetrapeptide mimetic farnesyl transferase inhibitors B956 (22) and B957 (23) are described. The two double bonds in 22 and 23 were constructed by application of iterative NHK and cuprate S(N)2' reactions. Normal syn NHK reaction and substrate-dependent syn and anti-S(N)2' diastereoselectivities accompanied by exclusive E-olefin selectivity were observed for the first NHK iteration (1 → 4). In the second iteration, unexpected epimerization and a strong preference for syn diastereoselectivity was observed for the NHK reaction (5b → 7a + 9a) while an unusual Z-olefin was observed for the S(N)2' reaction (7b → 11). Deprotection conditions were optimized to ensure high purity and yield of the final aminothiol compounds.
Enantioselective aldol chemistry via alkyl enol ethers. Scope of the Lewis acid catalyzed condensation of optically active trimethylsilyl and methyl 2-[(E)-1-alkenyloxy]ethanoates with acetals
Faunce, James A.,Grisso, Bryan A.,Mackenzie, Peter B.
, p. 3418 - 3426 (2007/10/02)
Optically active, mono- and disubstituted trimethylsilyl 2-[(E)-1-alkenyloxy]ethanoates of the type RR1CH = CHOCHR2CO2SiMe3 (R = Me, PhCH2, n-Bu, MeO2CCMe2CH2, PhSCHs
Synthetic and Enzyme Inhibition Studies of Pepstatin Analogues Containing Hydroxyethylene and ketomethylene Dipeptide Isosteres
Holladay, Mark W.,Salituro, Francesco G.,Rich, Daniel H.
, p. 375 - 383 (2007/10/02)
Synthetic details for the preparation of a series of hydroxyethylene and ketomethylene dipeptide isosteres with control of stereochemistry at C(2) are described.Incorporation of the isosteres into peptide sequences derived from pepstatin afforded potent inhibitors of the aspartic protease porcine pepsin.When or was substituted with statine ((3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid), inhibitors equipotent to the parent compound were obtained, whereas was a much less effective replacement for statine.A similar trend was evident in the corresponding ketones.The finding that structural features for good substrates do not closely parallel those for good inhibitors is discussed.
Enantiomerically Pure Building Blocks for Syntheses from Branched Malates
Aebi, Johannes D.,Sutter, Marius A.,Wasmuth, Daniel,Seebach, Dieter
, p. 2114 - 2126 (2007/10/02)
Isocitric acid lactone (13) and the chiral building blocks (2S,3R)-4-bromo-1,2-epoxy-3-methyl-butane (21), cis- and trans 2,3-epoxy-2-methylsuccinates (23, 24), and the singly protected (2R)-2-methyl-, -2-allyl- and -2-benzyl-1,3-propanediols (32a, b, c)
