Application of aziridinium ring opening for preparation of optically active diamine and triamine analogues: highly efficient synthesis and evaluation of DTPA-based MRI contrast enhancement agents

Abstract

Ring opening of aziridinium ions with nitrogen nucleophiles was applied to the highly efficient synthesis of optically active vicinal diamines and diethylene triamine pentaacetic acid (DTPA) analogues as potential magnetic resonance imaging (MRI) contrast enhancement agents. The synthetic method features a column-free isolation of the regiospecific and stereospecific nucleophilic substitution products of enantiomerically enriched aziridinium ions in excellent yield.

Directed, Palladium(II)-Catalyzed Enantioselective anti-Carboboration of Alkenyl Carbonyl Compounds

“…NMR spectra were recorded on Bruker AV-400, DRX-500 and AV-600 instruments. 1 H and 13 C spectra were internally referenced to SiMe 4 or solvent signals. The following abbreviations (or combinations thereof) were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, sept = septet, m = multiplet.…”

“…7 Purification using silica gel column chromatography with 1:1 hexanes:EtOAc as the eluent gave the product as a yellow solid (289 mg, 76% yield). 1 H NMR (600 MHz, CDCl 3 ) δ 8.95 (t, J = 2.0 Hz, 1H), 8.73 (d, J = 2.0 Hz, 2H), 7.74 (dt, J = 7.9, 0.9 Hz, 1H), 7.66 (dd, J = 8.2, 0.8 Hz, 1H), 7.41-7.37 (m, 2H), 7.33 (ddd, J = 7.9, 7.1, 0.9 Hz, 1H), 4.56 (p, J = 7.1 Hz, 1H), 4.34 (dd, J = 9.4, 8.5 Hz, 1H), 4.03 (dd, J = 8.4, 7.4 Hz, 1H), 3.19 (ddd, J = 14.8, 6.4, 1.1 Hz, 1H), 2.97 (dd, J = 14.8, 7.1 Hz, 1H), 2.03 (d, J = 1.2 Hz, 3H); 13 The title compound was prepared from L23 (214 mg, 1 mmol) and 1,2,3,4,5-pentafluoro-6-(trifluoromethyl)benzene (472 mg, 2 mmol) according to a literature procedure. 12 Purification using silica gel column chromatography with 2:1 hexanes:EtOAc as the eluent gave the product as a yellow solid (301 mg, 70% yield).…”

“…12 Purification using silica gel column chromatography with 2:1 hexanes:EtOAc as the eluent gave the product as a yellow solid (301 mg, 70% yield). 1 H NMR (600 MHz, CDCl 3 ) δ 7.69 (d, J = 7.8 Hz, 1H), 7.34-7.27 (m, 2H), 7.14 (dd, J = 7.0, 3.9 Hz, 1H), 7.08 (s, 1H), 4.52 (q, J = 7.6 Hz, 1H), 4.26 (t, J = 9.0 Hz, 1H), 4.00 (t, J = 7.9 Hz, 1H), 3.22 (dd, J = 14.8, 5.4 Hz, 1H), 2.89 (dd, J = 14.8, 8.0 Hz, 1H), 1.99 (s, 3H); 13 C NMR (150 MHz, CDCl 3 ) δ 165.4, 144.9 (dd, J C-F = 260.5, 14.9 Hz), 142.6 (dd, J C-F = 255.1, 14.3 Hz), 136.0, 129.0, 125.4, 123.8, 122.6 (t, J C-F = 13.3 Hz), 121.6, 120.7 (q, J C-F = 275.3 Hz), 119.5, 116.5, 110.8 (t, J C-F = 2.7 Hz), 108.0 (dtd, J C-F = 47.8, 35.1, 12.6 Hz), 72.1, 66.0, 31.0, 13.9; Benzyl protection: 13 A solution of benzyl bromide (1.88g, 11 mmol) in MeCN (1 mL) was prepared and added dropwise to a solution of L-tryptophanol (S1, 950 mg, 5 mmol) and K 2 CO 3 (1.5 g, 11 mmol) in MeCN (10 mL) at 0 ºC. The reaction mixture was filtered, concentrated under vacuum, and purified by silica gel column chromatography (4:1 hexanes:EtOAc) to afford 900 mg (48% yield) of S2.…”

Design, Synthesis, and Biological Evaluation of Polyaminocarboxylate Ligand‐Based Theranostic Conjugates for Antibody‐Targeted Cancer Therapy and Near‐Infrared Optical Imaging

“…against HeLa and colon cancer cells than the clinically available DFO. [17,18] Within our continued effort toward the development of metal chelation chemistry for cancert herapeutic and imaging applications, [17][18][19][20][21][22] we were interested in using the NE3TA-based cytotoxic agent for construction of am ultifunctional conjugate that can target, detect,a nd destroy cancerc ells. Development of such tumor-specific theranostic agents that combine the advantageso ft herapeutic and imaging components into as ingle platform remains an active area of cancer research.…”

Copper-Catalyzed Diamination of Unactivated Alkenes With Electron-Rich Amino Sources

“…After an SET process between complex A and 4-bromomorpholine, the formed Cu­(II) intermediate B could undergo a reaction sequence as proposed in our previous work, which involves nitrogen radical addition to an olefin, the formation of a Cu­(III) complex via a recombination of the resultant carbon radical and Cu­(II), and reductive elimination to deliver the vicinal bromoamine C . The subsequent S N 2 substitution reaction of the bromo atom by an adjacent N-atom formed the aziridinium intermediate D , which could undergo ring-opening with an external alkylamine to give the cis -product (Scheme , path a). An alternative reaction pathway (Scheme , path b) involving the ligand exchange of the Cu­(II) intermediate B with an external alkylamine to E and a reductive elimination of the Cu­(III) complex to forge the C sp3 –N bond could be ruled out as the anticipated product should be of a trans -configuration with external alkylamine installed at the β-position, which did not match with the experimental results.…”