Antineoplastic Agents, 120. Pancratium littorale

Abstract

The bulbs of Pancratium littorale collected in Hawaii were found to contain a new phenanthridone biosynthetic product designated pancratistatin (4a) that proved to be effective (38-106% life extension at 0.75-12.5 mg/kg dose levels) against the murine P-388 lymphocytic leukemia. Pancratistatin also markedly inhibited (ED50, 0.01 microgram/ml) growth of the P-388 in vitro cell line and in vivo murine M-5076 ovary sarcoma (53-84% life extension at 0.38-3.0 mg/kg). An X-ray crystal structure determination of pancratistatin monomethyl ether (4c) and a detailed high resolution (400 MHz) nmr study of pancratistatin and its pentaacetate (4b) completed assignment of structure 4a. Companion antineoplastic constituents of P. littorale were found to be narciclasine (2c) and its 7-deoxy derivative (2a). The structure of 7-deoxynarciclasine (2c) was also confirmed by an X-ray crystallographic analysis.

Studies toward the synthesis of Amaryllidaceae alkaloids from Morita-Baylis-Hillman adducts: a straightforward synthesis of functionalized dihydroisoquinolin-5(6H)-one core

“…IR ν max /cm 18.1,25.7,51.6,72.3,100.9,107.4,107.7,120.6,123.5,136.6,143.9,146.7,147.3,166.3;HRMS (EI,70eV) (±)-2- [1, methyl]prop -2-en-1-ol (16) To a solution of silyl ether 15 (0.35 g, 1 mmol) in anhydrous dichloromethane, at -78 °C and under an atmosphere of argon, was added of solution 1.0 mol L -1 of DIBAL-H (2.4 mL, 2.4 mmol) The reaction mixture was stirred for 2 h at -78 °C. After this time, a saturated solution of sodium acetate was added and the reaction mixture was dropped into a mixture of ethyl ether (50 mL) and a saturated solution of NH 4 Cl (4.6 mL).…”

“…IR ν max /cm 2, 18.5, 26.0, 63.4, 77.3, 101.2, 106.9, 108.1, 112.0, 119.6, 136.9, 147.0, 147.8, 150.7 [1,3]dioxol (17) To a solution of silyl ether 16 (0.68 g, 2.12 mmol) in 15 mL of dry dichloromethane, under an atmosphere of argon, was added anhydrous triethylamine (0.6 mL, 4.24 mmol), followed by triisopropylsilyl triflate (0.74 mL, 2.75 mmol). The resulting mixture was stirred for 1 h at room temperature.…”

“…1 Among the chemical constituents present in these plants, the alkaloids are the most important and, normally, they are responsible for the biological activities exhibited. As a matter of fact, the biological importance of the plants from this family led to an intense phytochemical research activity, which culminated with the isolation and chemical characterization of several structurally different classes of alkaloids.…”

“…Besides structural complexity, these alkaloids exhibit different biological activities. Galantamine (1), for example, is a specific, competitive and reversible acetyl cholinesterase inhibitor, being used in the clinical treatment of Alzheimer disease. 3 Pancratistatin (2), narciclasine (3), hippadine (4) and anhydrolycorinone (5) exhibit antiproliferative activity.…”

“…The organic layer was separated, dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by flash silica gel column chromatography (hexane/ethyl acetate 5%) to provide 39 as colorless viscous oil in 93% yield.IR ν max /cm -1 : 2954, 2929, 2856, 1613, 1473, 1232, 1109, 1069, 1040, 874, 836 -4.7, 18.2, 19.3, 25.8, 26.8, 63.5, 73.6, 101.5, 108.5, 110, 111.7, 112.4, 127.4, 129.4, 133.5, 135.3, 135.5, 147.3, 147.3, 149 (±)- [1,3] …”