反应详情

Treatment of 21 (0.71 g, 0.61 mmol), 1, 3-propanedithiol (1.26 mL, 12.55 mmol) in pyridine (43 mL) and H2O (6.1 mL) with TEA (1.28 mL, 9.15 mmol) according to the general procedure for azide reduction and introduction of C-4″ moiety gave free amine (0.69 g, 99%). Treatment of the free amine (0.47 g, 0.41 mmol) in DMF (20 mL) with 3-hydroxyisovaleric acid (88 μL, 0.82 mmol) which was activated with HOAt (0.23 g, 1.64 mmol) and HATU (0.62 g, 1.64 mmol) in DMF (10 mL) for 1 h, and then added DIPEA (5.71 mL, 3.28 mmol) gave compound 22 as colorless oil (0.32 g, 63%) and its α-isomer (76 mg, 15%). Rf=0.26 (Hexane/EtOAc, 1:1, v:v). [α]27D=+ 9.4 (CHCl3, c=2.8 mg/mL). 1H NMR (500 MHz, CDCl3): δ 0.73 (d, 3H, J5,6=5.5 Hz, H-6c), 1.09 (s, 3H, (CH3)2C(OH)CH2C(O)NH), 1.12 (d, 3H, J5,6=6.0 Hz, H-6b), 1.18 (s, 3H, (CH′3)2C(OH)CH2C(O)NH), 1.24 (d, 3H, J5,6=5.5 Hz, H-6a), 1.74 (m, 2H, OCH2CH2CH2NHZ), 1.99 (d, 1H, J=15.0 Hz, (CH3)2C(OH)CH2C(O)NH), 2.09 (d, 1H, J=15.0 Hz, (CH3)2C(OH)CH′2C(O)NH), 2.91 (m, 1H, H-5c), 2.98 (t, 1H, J1,2=8.0, J2,3=8.5 Hz, H-2c), 3.15 (t, 1H, J2,3=8.5, J3,4=9.0 Hz, H-3c), 3.22 (m, 2H, OCH2CH2CH2NHZ), 3.38 (s, 3H, OCH3), 3.39 (m, 2H, OCH2CH2CH2NHZ, 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=9.5 Hz, H-4a), 3.67 (m, 2H, OCH′2CH2CH2NHZ, H-5a), 3.76 (m, 1H, H-5b), 4.12 (dd, 1H, J2,3=3.5, J3,4=9.0 Hz, H-3b), 4.21 (dd, 1H, J2,3=3.0, J3,4=9.0 Hz, H-3a), 4.34 (d, 1H, J1,2=8.0 Hz, H-1c), 4.48 (d, 1H, J=11.0 Hz, PhCH2), 4.54 (d, 1H, J=11.0 Hz, PhCH′2), 4.60 (d, 1H, J=10.5 Hz, PhCH″2), 4.71 (d, 1H, J=12.5 Hz, PhCH′″2), 4.77 (s, 1H, H-1a), 4.83 (d, 1H, J=11.5 Hz, PhCH″″2), 4.85 (broad, 1H, NH), 4.95 (d, 1H, J=11.0 Hz, PhCH′″″2), 5.00 (s, 2H, PhCH2OC(O)), 5.15 (s, 1H, H-1b), 5.30 (d, 1H, J2,3=3.0 Hz, H-2a), 5.39 (d, 1H, J2,3=3.5 Hz, H-2b), 7.14-8.00 (m, 30H, Harom); 13C NMR (75 MHz, CDCl3): δ 17.7 (C-6c), 17.8 (C-6b), 18.1 (C-6a), 29.2 (OCH2CH2CH2NHZ), [29.3, 29.7 ((CH3)2C(OH)CH2C(O)NH)], 38.5 (OCH2CH2CH2NHZ), 47.7 ((CH3)2C(OH)CH2C(O)NH), 55.7 (C-4c), 60.3 (OCH3), 65.6 (OCH2CH2CH2NHZ), 66.6 (PhCH2OC(O)), 67.9 (C-5a), 68.6 (C-5b), 69.4 ((CH3)2C(OH)CH2C(O)NH), 70.6 (C-5c), 72.8 (C-2a), 73.1 (C-2b), [73.5, 74.1, 75.5 (PhCH2)], 76.1 (C-3b), 78.1 (C-3a), 79.8 (C-3c), 80.0 (C-4a), 80.5 (C-4b), 84.4 (C-2c), 97.1 (C-1a), 99.2 (C-1b), 103.0 (C-1c), [127.5, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 129.7, 129.8, 129.9, 130.2, 133.0, 133.3, 137.9, 138.3, 138.5 (Carom)], 156.4 (PhCH2OC(O)), [165.6, 165.9 (PhC(O)O)], 172.2 ((CH3)2C(OH)CH2C(O)NH); MALDI-TOF/MS: m/z: found [M+Na]+ 1261.4, MALDI-FTICR/MS: m/z: found [M+Na]+ 1261.5427, C70H82N2O18 calcd for [M+Na]+ 1261.5460.