1. Piperidine dispiro-1,2,4-trioxane analogues
Sunil Sabbani, Paul A Stocks, Gemma L Ellis, Jill Davies, Erik Hedenstrom, Stephen A Ward, Paul M O'Neill Bioorg Med Chem Lett. 2008 Nov 1;18(21):5804-8. doi: 10.1016/j.bmcl.2008.09.052. Epub 2008 Sep 17.
Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2) catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc 1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride salt 3 which was subsequently used to prepare derivatives (4-7). Several of these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the 3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a versatile derivative for the preparation of achiral arrays of trioxane analogues with antimalarial activity.
2. Au(III) complexes with tetradentate-cyclam-based ligands
Ann Christin Reiersølmoen, Thomas N Solvi, Anne Fiksdahl Beilstein J Org Chem. 2021 Jan 19;17:186-192. doi: 10.3762/bjoc.17.18. eCollection 2021.
Chiral cyclam (1,4,8,11-tetraazacyclotetradecane) derivatives were synthesized stepwise from chiral mono-Boc-1,2-diamines and (dialkyl)malonyl dichloride via open diamide-bis(N-Boc-amino) intermediates (65-91%). Deprotection and ring closure with a second malonyl unit afforded the cyclam tetraamide precursors (80-95%). The new protocol allowed the preparation of the target cyclam derivatives (53-59%) by a final optimized hydride reduction. Both the open tetraamine intermediates and the cyclam derivatives successfully coordinated with AuCl3 to give moderate to excellent yields (50-96%) of the corresponding novel tetra-coordinated N,N,N,N-Au(III) complexes with alternating five- and six-membered chelate rings. The testing of the catalytic ability of the cyclam-based N,N,N,N-Au(III) complexes demonstrated high catalytic activity of some complexes in selected test reactions (full conversion in 1-24 h, 62-97% product yields).
3. Crystal Structure Analysis of 4-Oxo, 4-hydroxy- and 4-alkyl-7-bromopyrazolo[5,1- c][1,2,4]triazines
Sergey M Ivanov, Denis S Koltun J Chem Crystallogr. 2022 Dec 17;1-12. doi: 10.1007/s10870-022-00973-x. Online ahead of print.
The crystal structures of 8-R1-7-bromo-3-tert-butyl-1-R2-pyrazolo[5,1-c][1,2,4]triazin-4(1H)-ones 1a-c, 2a,c (R1 = CN, CO2Et, NO2, R2 = H, 1:1 and 3:1 solvates with DMSO; R1 = CN, CO2Et, R2 = CH2Boc), 8-R1-7-bromo-3-tert-butyl-1-R2-1,4-dihydropyrazolo[5,1-c][1,2,4]triazin-4-ols 3a,b (R1 = CN, R2 = n-Bu; R1 = Br, R2 = CH2Boc), 1,4-dihydro- and aromatic 7-R3-3-tert-butyl-4-R4-8-methylpyrazolo[5,1-c][1,2,4]triazines 5a,b, 6 (R3 = H, R4 = n-Pr; R3 = Br, R4 = n-Bu) were investigated by X-ray diffraction analysis. The structural preferences and different packing modes based on the intermolecular interactions were analyzed by the Hirshfeld surface and energy framework analysis. Graphical abstract: The crystal structures of ten 3-tert-butyl-4-oxo, 4-hydroxy- and 4-alkyl-7-bromopyrazolo[5,1-c][1,2,4]triazines including non-solvated, 1:1 and 3:1 solvates with DMSO were investigated by single crystal X-ray diffraction, Hirshfeld surface and energy framework analyses. Supplementary information: The online version contains supplementary material available at 10.1007/s10870-022-00973-x.
