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Organic & Biomolecular Chemistry
H-38′), 4.25 (dd, J = 18.5 and 4.0 Hz, H-29′β) 4.18 (d, J = 14.3 H-20′α and H-46′β), 2.71 (d, J = 16.8 Hz, 1H, H-8α), 2.63 (s, 3H,
Hz, 1H, H-9′α), 4.02 (d, J = 12.8 Hz, H-20′β), 3.94 (dd, J = 18.5 H-23), 2.55 (s, 1H, H-19), 2.42 (q, J = 9.0 Hz, 1H, H-10β),
and 4.0 Hz, H-29′α), 3.78 (s, 3H, H-22), 3.78 (s, 3H, H-25), 3.76 2.14–2.06 (m, 3H, H-11α, H-1′α and H-33′α), 2.03 (s, 3H, H-27),
(s, 1H, H-2), 3.75 (s, 3H, H-26′), 3.72 (s, 3H, H-44′), 3.68 (d, J = 2.00–1.96 (m, 1H, H-33′β), 1.94–1.85 (m, 2H, H-34′), 1.80–1.73
5.0 Hz, 1H, H-1′β), 3.62–3.58 (m, 1H, H-32′α), 3.57 (s, 3H, (m, 5H, H-2′, H-21′, H-39′ and H-11), 1.72–1.66 (m, 1H, H-20β),
H-24′), 3.43 (d, J = 13.8 Hz, 1H, H-5′β), 3.38–3.35 (m, 1H, 1.37–1.22 (m, 2H, H-20α and H-40′β), 1.06–0.95 (m, 1H,
H-32′β), 3.34 (dd, J = 16.8 and 4.9 Hz, 1H, H-8β), 3.28 (td, J = H-40′α), 0.85 (t, J = 8.0 Hz, 3H, H-22′), 0.79–0.70 (m, 6H, H-41′
10.0 and 4.0 Hz, 1H, H-10α), 3.07 (d, J = 16.8 Hz, 1H, H-5′α), and H-42′), 0.67 (t, J = 8.1 Hz, 3H, H-21). 13C NMR (150 MHz,
2.85 (dd, J = 14.0 and 3.5 Hz, 1H, H-20′α), 2.78 (d, J = 16.8 Hz, CDCl3): δ 174.2 (C-23′), 172.0 (C-43′), 171.9 (C-24), 171.8
1H, H-8α), 2.70 (s, 3H, H-23), 2.61 (s, 1H, H-19), 2.47 (q, J = 9.0 (C-36′), 171.1 (C-25′), 171.0 (C-47′ and C-55′), 170.8 (C-26),
Hz, 1H, H-10β), 2.32–2.28 (m, 1H, H-11β), 2.22–2.13 (m, 2H, 170.7 (C-36′), 167.3 (C-27′), 167.0 (C-30′), 158.0 (C-16), 154.4
H-1′α and H-33′α), 2.08 (s, 3H, H-27), 1.94–1.84 (m, 3H, H-33′β (C-7′), 153.2 (C-18), 137.6 (C-4′), 135.1 (C-16′), 130.7 (C-18′),
and H-34′), 1.71–1.85 (m, 1H, 11α), 1.70–1.59 (m, 4H, H-21′, 129.4 (C-6), 129.1 (C-11′), 128.7, 128.6, 128.5 (C-49′-C-54′ and
H-39′), 1.53–1.51 (m, 1H, H-2′), 1.42–1.29 (m, 3H, H-20α, H-20β H-57′-H-62′), 124.8 (C-7), 124.3 (C-14), 123.4 (C-13), 123.2
and H-40′β), 1.19–1.13 (m, 1H, H-40′α), 0.94 (t, J = 8.0 Hz, 3H, (C-3′), 122.4 (C-14′), 120.7 (C-15), 120.3 (C-12′), 119.4 (C-13′),
H-22′), 0.91–0.84 (m, 6H, H-41′ and H-42′), 0.74 (t, J = 8.1 Hz, 115.7 (C-10′), 115.0 (C-8′), 110.5 (C-15′), 94.3 (C-17), 83.4 (C-2),
3H, H-21). 13C NMR (150 MHz, CD3CN): δ 175.4 (C-23′), 173.3 79.7 (C-3), 76.4 (C-4), 67.8 (C-48′), 67.1 (C-56′), 66.0 (C-19), 60.4
(C-43′), 173.1 (C-24), 172.7 (C-36′), 172.4 (C-25′), 171.8 (C-26), (C-35′), 58.0 (C-38′), 56.1 (C-19′), 55.9 (C-22), 54.3 (C-20′), 53.3
168.6 (C-30′), 166.7 (C-27′), 159.3 (C-16), 156.6 (C-7′), 154.4 (C-12), 52.6 (C-25), 52.5 (C-24′), 52.3 (C-26′), 50.7 (C-8), 50.5
(C-18), 139.5 (C-4′), 136.6 (C-16′), 132.4 (C-18′), 131.5 (C-6), (C-10), 50.0 (C-5′), 48.5 (C-45′), 46.6 (C-32′), 44.9 (C-11), 42.8
130.2 (C-11′), 125.9 (C-14), 125.6 (C-7), 124.6 (C-13), 123.9 (C-5), 42.2 (C-29′), 38.3 (C-39′), 38.0 (C-23), 37.6 (C-2′), 36.3
(C-3′), 122.9 (C-14′), 121.9 (C-15), 120.7 (C-12′), 120.0 (C-13′), (C-46′), 34.5 (C-1′), 30.9 (C-20), 29.8 (C-34′), 27.6 (C-21′), 25.0
115.8 (C-10′), 114.3 (C-8′), 112.3 (C-15′), 95.1 (C-17), 84.2 (C-2), (C-33′), 24.9 (C-9′), 24.8 (C-40′), 21.3 (C-27), 15.4 (C-42′), 12.2
79.8 (C-3), 77.5 (C-4), 66.0 (C-19), 61.2 (C-35′), 57.9 (C-19′), 57.0 (C-41′), 11.6 (C-22′), 11.5 (C-40′), 8.7 (C-21). HRMS-ESI calcd for
(C-38′), 55.2 (C-20′), 54.4 (C-12), 53.0 (C-44′), 52.9 (C-24′), 52.8 C81H97N8O11 1469.6915, found 1469.5588.
(C-25), 52.8 (C-26′), 51.3 (C-8), 50.9 (C-10), 50.9 (C-5′), 47.5
Hybrid 25. General procedure C was followed using NaBH
(C-32′), 45.9 (C-11), 43.9 (C-5), 42.7 (C-29′), 38.9 (C-23), 38.2 (OAc)3 (6 mg, 0.028 mmol, 3 eq.) and enamino ester 22 (10 mg,
(C-39′), 35.7 (C-2′), 34.9 (C-1′), 30.6 (C-20), 29.5 (C-34′), 28.4 0.009 mmol, 1 eq.) in dichloromethane (0.1 mL) at 0 °C. The
(C-21′), 26.2 (C-9′), 26.1 (C-40′), 25.7 (C-33′), 21.5 (C-27), 16.3 reaction mixture was stirred for 4 hours at 0 °C. The resulting
(C-42′), 12.8 (C-22′), 12.1 (C-41′), 8.9 (C-21). HRMS-ESI calcd for mixture was diluted with dichloromethane and washed with a
C64H82N7O15 1188.5863, found 1188.5980.
saturated sodium carbonate solution. Solvent removal under
Hybrid 24. General procedure B was followed using alkyne reduced pressure provided pure amino ester 25 (6 mg, 60%
21 (42 mg, 0.06 mmol, 2 eq.) and vinorelbine (24 mg, yield) as a white powder. [α]2D5 = −21 (c 0.1, CHCl3). 1H NMR
0.03 mmol, 1 eq.) in 0.5 mL of anhydrous acetonitrile. After (500 MHz, CDCl3) δ 8.01 (s, 1H, H-17′), 7.46 (d, J = 7.9 Hz, 1H,
2 h of stirring at room temperature, the solvent was evaporated H-12′), 7.07–6.94 (m, 4H, H-13′-H-15′ and H-28′), 6.51 (s, 1H,
under reduced pressure. The resulting residue was purified by H-14), 6.07 (s, 1H, H-17), 5.76 (dd, J = 10.1 and 5.1 Hz, 1H,
column chromatography on silica gel using ethyl acetate– H-7), 5.43 (s, 1H, H-4), 5.20 (d, J = 10.1 Hz, 1H, H-6), 5.06 (d,
acetone (1 : 0 to 4 : 1) to afford compound 24 (12 mg, 26% J = 4.7 Hz, 1H, H-3′), 4.45 (dd, J = 7.9 and 2.6 Hz, 1H, H-35′),
1
yield) as a yellow powder. [α]2D5 = −25 (c 0.1, CHCl3). H NMR 4.31 (dd, J = 16.6 and 6.1 Hz, 1H, H-29′α), 3.89 (d, J = 16.5 Hz,
(500 MHz, CDCl3) δ (ppm) 7.89 (s, 1H, H-17′), 7.47 (d, J = 8.0 1H, H-9′β), 3.82 (dd, J = 18.2 and 5.0 Hz, H-29′β), 3.74 (s, 3H,
Hz, 1H, H-11′), 7.29–7.15 (m, 10H, H-50′-H-54′ and H-58′- H-22), 3.73 (s, 3H, H-25), 3.72 (s, 3H, H-26′), 3.70–3.68 (m, 1H,
H-62′), 7.01–6.93 (m, 3H, H-14′, H-15′, H-37′), 6.90 (t, J = 8.0 H-20′β), 3.68 (s, 1H, H-2), 3.66–3.63 (m, 1H, H-8′), 3.65 (s, 3H,
Hz, 1H, H-13′), 6.87–6.82 (m, 1H, H-44′), 6.67 (br s, 1H, H-28′), H-37′), 3.62–3.56 (m, 1H, H-32′), 3.56 (s, 3H, H-24′), 3.52–3.48
6.60 (s, 1H, H-14), 6.04 (s, 1H, H-17), 5.77 (dd, J = 10.0 and 4.5 (m, 1H, H-20′α), 3.46–3.41 (m, 2H, H-7′ and H-9′α), 3.37–3.33
Hz, 1H, H-7), 5.40 (s, 1H, H-4), 5.21 (d, J = 10.0 Hz, 1H, H-6), (m, 3H, H-8α and H-5′), 3.36–3.29 (m, 1H, H-1′β), 3.30–3.25 (m,
5.10 (br s, 1H, H-3′), 5.03 (dd, J = 16.4 and 13.1 Hz, 2H, H-48′), 1H, H-8β), 3.20–3.17 (m, 1H, H-32′), 2.82–2.78 (m, 1H, H-10β),
4.97 (q, J = 12.3 Hz, 2H, H-56′), 4.85–4.81 (m, 1H, H-45′), 4.42 2.76 (d, J = 15.0 Hz, 1H, H-5′α), 2.69 (s, 3H, H-23), 2.67–2.59
(d, J = 14.1 Hz, 1H, H-9′β), 4.40 (d, J = 7.0 Hz, 1H, H-35′), 4.18 (m, 2H, H-34′), 2.61 (s, 1H, H-19), 2.40 (td, J = 9.8 and 7.3 Hz,
(m, 2H, H-29′β and H-38′), 4.10 (d, J = 14.1 Hz, 1H, H-9′α), 3.95 1H, H-10α), 2.34–2.29 (m, 3H, H-1′α and H-11), 2.02–1.95 (m,
(d, J = 12.8 Hz, H-20′β), 3.88 (dd, J = 18.3 and 3.6 Hz, H-29′α), 3H, H-33′), 1.91–1.80 (m, 2H, H-21′), 1.82–1.75 (m, 1H, H-20β),
3.72 (s, 3H, H-22), 3.71 (s, 3H, H-25), 3.69 (s, 1H, H-2), 3.67 (s, 1.37–1.30 (m, 1H, H-2′), 1.30 (s, 3H, H-27), 1.30–1.25 (m, 1H,
3H, H-26′), 3.53–3.50 (m, 2H, H-1′β and H-32′α), 3.50 (s, 3H, H-20α), 0.87 (t, J = 7.2 Hz, 3H, H-22′), 0.69 (t, J = 7.8 Hz, 3H,
H-24′), 3.37 (d, J = 13.8 Hz, 1H, H-5′β), 3.35–3.33 (m, 1H, H-21). 13C NMR (125 MHz, CDCl3) δ 175.1 (C-23′), 174.1
H-32′β), 3.30 (dd, J = 16.8 and 4.9 Hz, 1H, H-8β), 3.21 (td, J = (C-36′), 172.2 (C-24), 171.1 (C-25′), 170.4 (C-26), 167.2 (C-30′),
9.0 and 4.4 Hz, 1H, 10α), 3.04 (dd, J = 18.8 and 4.9 Hz, 1H, 163.7 (C-27′), 158.5 (C-16), 154.1 (C-18), 138.4 (C-4′), 134.5
H-46′α), 2.99 (d, J = 16.8 Hz, 1H, H-5′α), 2.84–2.76 (m, 2H, (C-16′), 131.8 (C-18′), 130.3 (C-6), 129.7 (C-11′), 125.7 (C-15),
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