反応手順
Treatment of 20 (21 mg, 0.018 mmol), 1,3-propanedithiol (0.04 mL, 0.40 mmol) in pyridine (1.28 mL) and H2O (0.92 mL) with TEA (0.03 mL, 0.27 mmol) according to the general procedure for azide reduction and introduction of C-4″ moiety gave free amine (20 mg, 98%). Treatment the free amine (20 mg, 0.018 mmol) in DMF (2 mL) with β-hydroxyisovaleric acid (4 μL, 0.037 mmol) which was activated with HOAt (10 mg, 0.074 mmol) and HATU (28 mg, 0.074 mmol) in DMF (1 mL) for 1 h, and then added DIPEA (26 μL, 0.15 mmol) gave compound 23 as colorless oil (17 mg, 78%). Rf=0.61 (Hexane/EtOAc, 1:2, v:v). 1H NMR (500 MHz, CDCl3): δ 0.79 (d, 3H, J5,6=6.5 Hz, H-6c), 1.11 (s, 3H, (CH3)2C(OH)CH2C(O)NH), 1.12 (d, 3H, J5,6=6.5 Hz, H-6b), 1.14 (s, 3H, (CH′3)2C(OH)CH2C(O)NH), 1.25 (d, 3H, J5,6=5.5 Hz, H-6a), 1.74 (m, 2H, OCH2CH2CH2NHZ), 2.06 (d, 1H, J=15.0 Hz, (CH3)2C(OH)CH2C(O)NH), 2.14 (d, 1H, J=15.0 Hz, (CH3)2C(OH)CH′2C(O)NH), 2.98 (m, 1H, H-5c), 3.21 (m, 3H, OCH2CH2CH2NHZ, H-3c), 3.36-3.42 (m, 3H, OCH2CH2CH2NHZ, H-2c, H-4c), 3.52 (t, 1H, J3,4=9.0, J4,5=9.5 Hz, H-4b), 3.54 (t, 1H, J3,4=9.0, J4,5=10.0 Hz, H-4a), 3.68 (m, 2H, OCH′2CH2CH2NHZ, H-5a), 3.77 (m, 1H, H-5b), 4.08 (dd, 1H, J2,3=3.0, J3,4=9.0 Hz, H-3b), 4.14 (d, 1H, J1,2=7.5 Hz, H-1c), 4.21 (dd, 1H, J2,3=3.0, J3,4=9.0 Hz, H-3a), 4.49 (d, 1H, J=11.0 Hz, PhCH2), 4.57 (d, 1H, J=11.0 Hz, PhCH′2), 4.60 (d, 1H, J=10.5 Hz, PhCH″2), 4.67 (d, 1H, J=11.0 Hz, PhCH′″2), 4.73 (d, 1H, J=11.0 Hz, PhCH″″2), 4.77 (s, 1H, H-1a), 4.86 (broad, 1H, NH), 4.94 (d, 1H, J=10.5 Hz, PhCH′″″2), 5.00 (s, 2H, PhCH2OC(O)), 5.13 (s, 1H, H-1b), 5.32 (d, 1H, J2,3=3.0 Hz, H-2a), 5.38 (d, 1H, J2,3=3.5 Hz, H-2b), 5.43 (d, 1H, J=9.0 Hz, (CH3)2C(OH)CH2C(O)NH), 7.19-8.02 (m, 30H, Harom); 13C NMR (75 MHz, CDCl3): δ 17.7 (C-6c), 17.9 (C-6b), 18.1 (C-6a), [29.3, 29.4 ((CH3)2C(OH)CH2C(O)NH)], 29.7 (OCH2CH2CH2NHZ), 38.5 (OCH2CH2CH2NHZ), 47.8 ((CH3)2C(OH)CH2C(O)NH), 55.3 (C-4c), 65.6 (OCH2CH2CH2NHZ), 66.6 (PhCH2OC(O)), 67.9 (C-5a), 68.7 (C-5b), 69.5 ((CH3)2C(OH)CH2C(O)NH), 70.9 (C-5c), 72.7 (C-2a), 72.8 (C-2b), [72.5, 74.6, 75.4 (PhCH2)], 74.9 (C-2c), 77.2 (C-3b), 78.0 (C-3a), 79.6 (C-3c), 80.0 (C-4a), 80.1 (C-4b), 97.1 (C-1a), 99.1 (C-1b), 103.1 (C-1c), [127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.6, 129.7, 129.8, 130.0, 133.1, 133.3, 137.9, 138.0, 138.4 (Carom)], 151.7 (PhCH2OC(O)), [165.7, 165.9 (PhC(O)O)], 172.3 ((CH3)2C(OH)CH2C(O)NH); MALDI-TOF/MS: m/z: found [M+Na]+ 1249.7, C69H80N2O18 calcd for [M+Na]+ 1247.5304.
