Narciclasine, an inhibitor of protein synthesis. Action onAllium cepa L. root meristems

Antineoplastic Agents. 527. Synthesis of 7-Deoxynarcistatin, 7-Deoxy-trans-dihydronarcistatin, and trans-Dihydronarcistatin 1

“…13a Downfield shifts for the H-3 and H-4 resonances displayed by 3,4-cyclic phosphates 5-8 were observed in all cases when compared with the spectra of each of the starting isocarbostyrils. The 1 H NMR spectrum of 7-deoxynarciclasine (1b) revealed the H-3 and H-4 resonances at δ 3.69 and 3.76, respectively, whereas the derived phosphate (5) showed H-3 and H-4 downfield as a multiplet at δ 3.93-3.79. In trans-dihydro derivative 3a, the multiplet at δ 3.69 was assigned to H-3 and H-4 and in cyclic phosphate 6 they were at δ 4.11 (H-3) and 4.03 (H-4).…”

“…The colorless product was collected (2. Sodium 7-Deoxynarcistatin (5). A solution of 7-deoxynarciclasine (1b, 0.2 g, 0.69 mmol) in pyridine (8 mL) was heated to 80 °C, and tetrabutylammonium dihydrogen phosphate (0.15 g, 0.45 mmol, 0.65 equiv) followed by dicyclohexylcarbodiimide (0.8 g, 5.6 equiv) were added.…”

“…Advances in the chemistry of isocarbostyrils were already being achieved in the 1909−1920 period by the well-known organic chemists Dieckmann,2a Robinson,2b Perkin,2b and Chichibabin 2c. However, interest in the potential of naturally occurring isocarbostyrils as anticancer agents only began with the isolation of narciclasine ( 1a ) − in 1967 and our cancer bioassay-directed discovery of pancratistatin ( 2 ) as a constituent of Pancratium littorale (now Hymenocallis littoralis , Amaryllidaceae) accompanied by narciclasine ( 1a ) and 7-deoxynarciclasine ( 1b , lycoricidine, margetine). Later, we isolated another new anticancer constituent from H. littoralis identified as 7-deoxy- trans -dihydronarciclasine ( 3a ) 10a.…”

“…Recrystallization of the precipitate (3b) from CH2Cl2-CH3-OH gave colorless needles: mp 208 °C, [R] 23 D +103°(c 0.53 CH2Cl2) [lit. 15b mp 148-149 °C]; 1 HNMR (CDCl3, 300 MHz) δ 7.55 (1H, s, H-7), 6.72 (1H, s, 1H), 6.18 (1H, s, NH), 6.03 (2H, s, -OCH 2O-),5.43 (1H, t, J ) 3 Hz, H-3), 5.22-5.18 (2H, m, H-3, H-4), 3.79 (1H, dd, J ) 12.75, 10.95, H-4a), 3.18 (1H, m, H-10b), 2.5 (1H, m, H-1eq), 2.07 (3H, s, -OCOCH3), 2.09 (3H, s, -OCOCH3), 2.14 (3H, s, -OCOCH3),1.94 (m, 1H, H-1ax);13 C NMR (DMSO-d6, 75 MHz) δ 169.8 (C, OCOCH3) 168.7 (C, OCOCH3), 168.6 (C, OCOCH3), 165.3 (C, C-6), 150.9 (C), 146.5 (C), 135.2 (C), 122.6 (C), 107.7 (CH, C-7), 103.4 (CH, C-10), 101.3 (CH 2, -OCH2O-), 70.9 (CH, C-4), 68.1 (CH, C-2), 67.0 (CH, C-3), 52.3 (CH, C-4a), 34.2 (CH, C-10b), 26.2 (CH, C-1), 20.5 (CH 3, -OCOCH3), 20.4 (CH3, -OCOCH3), 20.2 (CH3, -OCOCH3); HRAPCI + m/z 420.1282 [M + H] + (calcd for C20H21NO9 420.1294 [M + H] + ).…”

The Biochemistry of Alkaloids

“…Affected ribosomes are less efficient in synthesizing protein [60,63]. At concentrations in the range of 10-5 M, narciclasine inhibits growth of onion roots and causes mitotic aberrations [231]. It acts only on eukaryotic ribosomes, binding to the 60S subunit at the peptidyl transferase center so that access of the 3'-OH of the donor substrate is blocked and no peptide bond can be formed [14,39].…”