1.Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral-at-Rhodium Lewis Acid.
Huang Y1, Song L1, Gong L2, Meggers E3,4. Chem Asian J. 2015 Dec;10(12):2738-43. doi: 10.1002/asia.201500764. Epub 2015 Sep 7.
A bis-cyclometalated chiral-at-metal rhodium complex catalyzes the Diels-Alder reaction between N-Boc-protected 3-vinylindoles (Boc=tert-butyloxycarbonyl) and β-carboxylic ester-substituted α,β-unsaturated 2-acyl imidazoles with good-to-excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92-99 % ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2-acyl imidazole dienophile by two-point binding and overrules the preferred regioselectivity of the uncatalyzed reaction.
2.Proline functionalization of the mesoporous metal-organic framework DUT-32.
Kutzscher C1, Hoffmann HC, Krause S, Stoeck U, Senkovska I, Brunner E, Kaskel S. Inorg Chem. 2015 Feb 2;54(3):1003-9. doi: 10.1021/ic502380q. Epub 2014 Dec 9.
The linker functionalization strategy was applied to incorporate proline moieties into a metal-organic framework (MOF). When 4,4'-biphenyldicarboxylic acid was replaced with a Boc-protected proline-functionalized linker (H(2)L) in the synthesis of DUT-32 (DUT = Dresden University of Technology), a highly porous enantiomerically pure MOF (DUT-32-NHProBoc) was obtained, as could be confirmed by enantioselective high-performance liquid chromatography (HPLC) measurements and solid-state NMR experiments. Isotope labeling of the chiral side group proline enabled highly sensitive one- and two-dimensional solid-state (13)C NMR experiments. For samples loaded with (S)-1-phenyl-2,2,2-trifluoroethanol [(S)-TFPE], the proline groups are shown to exhibit a lower mobility than that for (R)-TFPE-loaded samples. This indicates a preferred interaction of the shift agent (S)-TFPE with the chiral moieties. The high porosity of the compound is reflected by an exceptionally high ethyl cinnamate adsorption capacity.
3.Synthetic 1,2,3-triazole-linked glycoconjugates bind with high affinity to human galectin-3.
Marchiori MF1, Souto DE2, Bortot LO1, Pereira JF1, Kubota LT2, Cummings RD3, Dias-Baruffi M1, Carvalho I1, Campo VL4. Bioorg Med Chem. 2015 Jul 1;23(13):3414-25. doi: 10.1016/j.bmc.2015.04.044. Epub 2015 Apr 28.
This work describes the synthesis of the 1,2,3-triazole amino acid-derived-3-O-galactosides 1-6 and the 1,2,3-triazole di-lactose-derived glycoconjugate 7 as potential galectin-3 inhibitors. The target compounds were synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-derived amino acids N3-ThrOBn, N3-PheOBn, N3-N-Boc-TrpOBn, N3-N-Boc-LysOBn, N3-O-tBu-AspOBn and N3-l-TyrOH, and the corresponding alkyne-based sugar 3-O-propynyl-GalOMe, as well as by click chemistry reaction between the azido-lactose and 2-propynyl lactose. Surface plasmon resonance (SPR) assays showed that all synthetic glycoconjugates 1-7 bound to galectin-3 with high affinity, but the highest binders were the amino acids-derived glycoconjugates 2 (KD 7.96μM) and 4 (KD 4.56μM), and the divalent lactoside 7 (KD1 0.15μM/KD2 19μM). Molecular modeling results were in agreement with SPR assays, since more stable interactions with galectin-3 were identified for glycoconjugates 2, 4 and 7.
4.Two Scalable Syntheses of (S)-2-Methylazetidine.
Dowling MS1, Fernando DP1, Hou J2, Liu B2, Smith AC1. J Org Chem. 2016 Apr 1;81(7):3031-6. doi: 10.1021/acs.joc.6b00149. Epub 2016 Mar 11.
Two orthogonal routes for preparing (S)-2-methylazetidine as a bench stable, crystalline (R)-(-)-CSA salt are presented. One route features the in situ generation and cyclization of a 1,3-bis-triflate to form the azetidine ring, while the second route involves chemoselective reduction of N-Boc azetidine-2-carboxylic acid. Both sequences afford the desired product in good overall yields (61% and 49%) and high enantiomeric excess (>99% ee), avoid column chromatography, and are suitable for the large-scale production of this material.
