Synthesis and evaluation of malonate-based inhibitors of phosphosugar-metabolizing enzymes: Class II fructose-1,6-bis-phosphate aldolases, type I phosphomannose isomerase, and phosphoglucose isomerase

Unprecedented formation of 8(R),5′-O-cycloribonucleosides through a triflation reaction of purine ribonucleosides

“…1 Over the past decades, several classes of phosphate ester mimics have been developed, especially in the field of nucleic acids and their components (e.g., phosphonates, 1d,2 boranophosphates, 3 sulfonates and sulfonamides, 4 dicarboxylates, 5 squarates, 6 and cyclic mimics 7 ) to confer membrane permeability and resistance to catabolic enzymes. The simplest and most investigated phosphate bioisostere is the methylene phosphonate, in which the hydrolyzable CeOeP bonding arrangement is replaced with the non-hydrolyzable CeCeP bonding arrangement.…”

Targeting Metalloenzymes for Therapeutic Intervention

“…1107,1108 Subsequent development of class II FBA inhibitors include substrate (DHAP) analogues or transition state mimics, but have largely maintained the use of a hydroxamic acid MBP with a phosphoglycolate skeleton. 1105,1107–1113 Inhibitors in this class include N -sulfonyl hydroxamate, hydrazine, hexitol bis-phosphate, and hydroxamate based derivatives (e.g., FBAi-1, FBAi-2, Figure 113), with the most potent inhibitors achieving K i value as low as 4 nM against FBA from various sources. 1105,1107,1108,1110–1112 In addition to the disadvantages of a hydroxamic acid MBP, the use of a polar phosphate group has also hindered the development of these inhibitors.…”

Methyl 6‐Amino‐6‐deoxy‐d‐pyranoside‐Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)‐Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism

“…The excess CH 3 CN was removed by evaporation, then the residue was subjected to column chromatography (petroleum ether/EtOAc, 6:1 then 2:1) to give 4 (0.27 g, 79 % yield) as a colorless oil: 1 H NMR (600 MHz, CDCl 3 ): δ= 7.31–7.23 (m, 10 H), 5.15 (s, 4 H), 3.93–3.91 (t, J =7.3 Hz, 1 H), 3.02 ppm (d, J =7.3 Hz, 2 H); 13 C NMR (150 MHz, CDCl 3 ): δ= 177.1, 168.0, 135.1, 128.7, 128.6, 128.3, 67.8, 47.7, 32.0 ppm. The structure was also confirmed by reported spectroscopic data …”

“…The resulting oil was subjected to column chromatography (petroleum ether/ EtOAc, 20:1) to give 3 (1.73 g, 92 %y ield) as ac olorless oil: 1 The structure was also confirmed by reported spectroscopic data. [40] Methyl 6-amino-6-deoxyglucopyranoside-conjugated dibenzylmalonate (8):C ompound 4 (0.34 g, 1.00 mmol) and N-hydroxysuccinimide (NHS;0 .13 g, 1.10 mmol) were dissolved in dry DMF (2.5 mL), then DCC (0.23 g, 1.10 mmol) was added. The reaction mixture was stirred at room temperature overnight.…”