Synthesis
Bis-(3-azido-3-deoxy-β-D-galactopyranosyl)-thiane (11) and 3-fluorophenylacetylene (3 eq.) were synthesized by cycloaddition reaction in the presence of a Cu(I) catalyst (0.2 eq.) and triethylamine (2 eq.) in N,N-dimethylformamide (DMF, 100 mL/mmol of thiane) under room temperature conditions TD139.The progress of the reaction was monitored by thin layer chromatography (TLC) until completion. After the reaction mixture was concentrated, it was first initially purified by fast column chromatography (eluent: CH2Cl2:MeOH, 8:1), followed by final purification by preparative high-performance liquid chromatography (HPLC) to afford TD139 in 76% yield as a white amorphous solid.1H-NMR (CD3OD, 400 MHz) δ 8.59 (s, 2H, triazole-H ), 7.63 (br d, 2H, J = 7.6 Hz, Ar-H), 7.57 (br d, 2H, J = 8.4 Hz, Ar-H), 7.41 (dt, 2H, J = 6.0, 8.0 Hz, Ar-H), 7.05 (br dt, 2H, J = 2.4, 6.4 Hz, Ar-H), 4.93 (dd, 2H, J = 2.4 , 10.4 Hz, H3), 4.92 (d, 2H, J = 10.4 Hz, H1), 4.84 (d, 2H, J = 10.4 Hz, H2), 4.18 (d, 2H, J = 2.4 Hz, H4), 3.92 (dd, 2H, J = 4.2, 7.6 Hz, H5), 3.84 (dd, 2H, J = 7.6, 11.4 Hz , H6), 3.73 (dd, 2H, J = 4.2, 11.4 Hz, H6); the FAB-HRMS m/z calculated value of C28H30F2N6NaO8S (M + Na+) was 671.1712 and the measured value was 671.1705.
References
[1] Patent: US2014/121179, 2014, A1. Location in patent: Paragraph 0188; 0200
[2] Patent: WO2014/78655, 2014, A1. Location in patent: Page/Page column 90; 94
[3] ChemBioChem, 2016, vol. 17, # 18, p. 1759 - 1770
