Eur. of regioisomers. Consequently, this response is of small worth,19 and just a few organized research on ring-opening reactions of vinyl fabric epoxides by azide ion have already been released.19-23 We achieved regioselective epoxide band openings of ,-epoxy-,-unsaturated esters 15 and 16 with Ti(O-configuration of alkene 21 was verified from the 1H NMR spectrum, which ultimately shows correlated two doublets ( 6.20 ppm, = 9.8 Hz, =C= 9.8 Hz, RCHCisomerization,27-30 it would appear that azide anion may play an identical part as pyridine inside our reaction. Reduced amount of an azide for an amine in the current presence of a dual bond isn’t trivial. Both Staudinger decrease (Ph3P, THF/H2O) and 1,3-propanedithiol/Et3N31 didn’t produce satisfactory outcomes. Decrease using Lindlars catalyst (H2, Pd/CaCO3, EtOH)32 led to saturation from the dual bond. Luckily, as illustrated in Structure 4, we discovered that simultaneous reduced amount of the azide and demethylation of methyl ester 17 was achieved by using SnCl2in 95% MeOH,33 offering 2 in 69% produce, as well as 22 (17% produce). Methyl ester 22 was changed to 2 by treatment with TMSBr in quantitative produce. Our new artificial path to 2 includes nine measures from commercially obtainable aldehyde 8 in 19% general produce. The azide analogue 5 was shaped by demethylation of 17 with TMSBr, accompanied by aqueous MeOH, inside a quantitative produce. The stereochemistry of 22 was verified by its particular rotation: []25D +20.0 (0.18, CHCl3) [lit.5 []25D +18.8 (1.52, CHCl3)]. Open up in another window Structure 4 Synthesis of 2 and 5. Fluorination of 17 with DAST34 (?78 C, overnight, and at rt for 3 h) produced 23 in 75% yield (Structure 4). Termination from the response at low temperatures led to imperfect conversion. As opposed to 17, reduced amount of 23 using Lindlars catalyst (H2, Pd/CaCO3, EtOH)32 didn’t reduce the dual bond, offering 24 in 51% produce. Demethylation of methyl esters 23 and 24 with TMSBr accompanied by 95% MeOH afforded the prospective fluorine-containing analogues 4 and 3, respectively, in quantitative produces. The unsaturated carboxylic acidity analogue 6 was made by reduced amount of 20 (SnCl2 in MeOH), accompanied by hydrolysis of ester 25 with LiOH in THF/MeOH/H2O. Catalytic SAR131675 hydrogenation of 21 (H2, Pd/C) offered lactone analogue 7 in 46% produce. 3. Biological evaluation We’ve shown that = 7.8 Hz, DNM1 2H), 2.72 (t, = 8.2 Hz, 2H), 2.99 (d, = 4.6 Hz, 1H), 3.04 (d, = 4.6 Hz, 1H), 7.10-7.13 (m, 4H), 8.89 (s, 1H); 13C NMR (125 MHz, CDCl3) 14.1, 22.6, 29.2, 29.3, 29.5, 29.9, 30.2, 31.5, 31.9, 35.5, 49.8, 60.9, 128.1, 128.5, 138.0, 140.8, 198.8; ESI-HRMS (M+Na)+ calcd for C19H28NaO2+ 311.1982, found 311.1986. 5.1.5. Planning of (= 5.4 Hz, 1H), 3.72 (d, = 5.5 Hz, 3H), 3.74 (d, = 5.5 Hz, 3H), 5.95 (dd, = 17.2, 19.4 Hz, 1H), 6.83 (dd, = 17.2, 22.2 Hz, 1H), 7.05-7.13 (m, 4H); 13C NMR (100 MHz, SAR131675 CDCl3) 14.1, 22.6, 29.2, 29.3, 29.4, SAR131675 30.6, 31.5, 31.8, 35.2, 35.5, 52.38 (d, = 5.4 Hz), 52.41 (d, = 5.4 Hz), 55.9, 58.2 (d, = 24.0 Hz), 116.5 (d, = 189.6 Hz), 128.0, 128.5, 137.9, 140.8, 151.6 (d, = 6.5 Hz); 31P NMR (162 MHz, CDCl3) 20.6; ESI-HRMS (M+H)+ calcd for C22H36O4P+ 395.2346, found 395.2346. 5.1.6. Planning of (= 7.7 Hz, 2H), 2.65-2.75 (m, 3H), 2.88 (d, = 5.4 Hz, 1H), 4.21 (q, = 7.1 Hz, 2H), 6.10 (d, = 15.7 Hz, 1H), 6.91 (d, = 15.7 Hz, 1H), 7.06-7.12 (m, 4H); 13C NMR (100 MHz, CDCl3) 14.1, 14.2, 22.6, 29.2, 29.3, 29.5, 30.7, 31.5, 31.9, 35.45, 35.52, 55.8, 57.6, 60.6, 122.2, 128.1, 128.5, 138.1, 140.8, 146.6, 166.0; ESI-HRMS (M+Na)+ calcd for C23H34NaO3+ 381.2400, found 381.2401. 5.1.7. Planning of (= 17.1, 19.3 Hz, 1H), 6.72.