ChemInform Abstract: Studies Directed Towards the Refinement of the Pancratistatin Cytotoxic Pharmacophore.

Abstract

Studies Directed Towards the Refinement of the Pancratistatin Cytotoxic Pharmacophore.-The preparation of the deoxy-analogue (VIIIb) of the anticancer/antiviral agent pancratistatin (VIIIa) containing functionality complementary to the minimum structural pharmacophore utilizing a Diels-Alder approach is described. Initial anticancer screening of the two deoxyanalogues (VIIIb) and (VIIIc) shows marginal activity for (VIIIc) and selective inhibition of certain tumor cell lines by (VIIIb), however, at a significantly lower level compared to the natural product (VIIIa). -(MCNULTY, JAMES; MAO, JUSTIN; GIBE, ROMELO; MO, RUOWEI; WOLF, SONJA; PETTIT, GEORGE R.; HERALD, DELBERT L.; BOYD, MICHAEL R.; Bioorg. Med. Chem. Lett. 11 (2001) 2, 169-172; Dep. Chem., Brock Univ., St. Catharines, Ont. L2S 3A1, Can.; EN)

Potential anti-proliferative effects of chemical constituents and hemisynthetic derivatives from Scadoxus pseudocaulus (Amarillydaceae)

“…13 7-deoxy-trans-dihydronarciclasin has significant anti-cancer effects and the detailed SAR studies elucidated that this molecule has pharmacophore moiety which induces apoptosis. 15,19,[36][37][38][39][40] The tri-hydroxyl-ated ring C of this compound is also considered to be a critical part. In fact, the substitution of tri-hydroxylated ring C with hydrophobic moieties led to decrease in anti-cancer capacity and the same was observed upon loss of three hydroxyl groups.…”

“…In fact, the substitution of tri-hydroxylated ring C with hydrophobic moieties led to decrease in anti-cancer capacity and the same was observed upon loss of three hydroxyl groups. 37,[41][42][43][44] Thus, it could be seen that 7-deoxy-trans-dihydronarciclasin has significant cytotoxic effects and can induce apoptosis in cancer cell lines making it a lead molecule in cancer research. The antiproliferative effects of sideroxylin against ovarian cancer cells are through the induction of mitochondrial dysfunction and the activation of PI3 K and MAPK signal transduction.…”

Synthesis and Biological Evaluation of Fully Functionalized seco-Pancratistatin Analogues

“…The pooled organic fractions were dried over anhydrous Na2SO4 and filtered to give an amorphous gum, which was subjected to column chromatography on silica gel with 50:50 EtOAc/hexane, affording diol 20 as a colorless oil in 88% yield. (10), 307 (15), 255 (15), 219 (25), 155 (30), 135 (100). 1 H NMR (700 MHz, CDCl3), δ 0.00 (6H, s, Si(CH3)2), 0.81 (9H, s, SiC(CH3)3), 1.31 (3H, s, O-C(CH3)2-O), 1.44 (3H, s, O-C(CH3)2-O), 2.96 (1H, ddd, J ) 5.6, 7.0, 9.8 Hz, H-2), 3.56 (1H, dd, J ) 3.5, 10.5 Hz, H-6a), 3.63 (1H, dd, J ) 5.6, 10.5 Hz, H-6b), 3.78 (1H, d, J ) 9.8 Hz, H-4), 3.84 (1H, dd, J ) 9.8, 9.8 Hz, H-3), 3.87 (1H, dd, J ) 7.0, 10.8 Hz, H-1a), 4.00 (1H, ddd, J ) 3.5, 5.6, 9.8 Hz, H-5), 4.07 (1H, dd, J ) 5.6, 10.8 Hz, H-1b), 5.92 (2H, s, OCH 2O), 6.67 (1H, dd, J ) 1.4, 8.0 Hz, H-5′), 6.71 (1H, d, J ) 1.…”

“…The combined organic fractions were dried over anhydrous Na2SO4 and filtered, and solvent was removed under vacuum to give an amorphous residue, which was columned on silica gel with 10:90 EtOAc/hexane, affording bromide 22 as a pale yellow oil in 70% yield. (15), 551 (10), 529 (25), 471 (13), 407 (5), 349 (17), 291 (18), 279 (23), 201 (15), 149 (45), 105 (100), 77 (34); 1 H NMR (600 MHz, CDCl3), δ -0.05 (6H, s, Si(CH3)2), 0.80 (9H, s, SiC(CH3)3), 1.30 (3H, s, O-C(CH3)2-O), 1.43 (3H, s, O-C(CH3)2-O), 3.56 (1H, ddd, J ) 5.0, 7.0, 9.6 Hz, H-2), 3.61 (1H, dd, J ) 7.0, 10.0 Hz, H-1a), 3.65 (1H, dd, J ) 5.0, 10.0 Hz, H-1b), 3.67 (1H, dd, J ) 4.8, 10.5 Hz, H-6a), 3.69 (1H, dd, J ) 6.5, 10.5 Hz, H-6b), 3.71 (1H, ddd, J ) 4.8, 6.5, 8. 4 Hz, H-5), 3.90 (1H, d, J ) 8.…”

Nitroalkenes as Amination Tools

“…A direct procedure to build up nitrocyclohexene units involved the Diels -Alder reaction between a nitrostyrene and butadiene (Scheme 3.67 ) [135] .…”