David E. Berry

The chemistry of toxic principles from Maytenus nemerosa

Abstract Maytenus nemerosa has been fractionated systematically by following the toxicity of extracts, partitioned solutions and column chromatographic fractions against cultured KB cells. Several compounds were isolated in this fashion, including 3-oxo-20(29)-lupen-30-al, β-amyrin, 29-hydroxyfriedelan-3-one, 30-hydroxy-20(29)-lupen-3-one, 30-hydroxyfriedelan-3-one and lup-20(29)-ene-3β,30-diol, as well as tingenone, 20-hydroxytingenone and galactitol. 3-Oxo-20(29)-lupen-30-al was shown to be cytotoxic for the first time; the structural basis of this cytotoxicity was investigated, in part, by bioassay of four products obtained by chemical transformation of single, isolated principles.

Afromontoside. A new cytotoxic principle from Dracaena afromontana

A new cytotoxic principle, steroidal saponin afromontoside (1), has been isolated from a methanolic extract of the twigs of Dracaena afromontana. It was shown to be (25R)-furost-5-ene-3β,22α,26-triol 26-O-α-L-rhamnopyranoside 3-O-([O-α-L-rhamnopyranosyl(1→4)]-β-D-glucopyranoside) by spectral and chemical methods. The aglycone of afromontoside, diosgenin, as well as dihydrodiosgenin and several structurally related compounds have been shown to be cytotoxic to cultured KB cells.

NEW DINUCLEAR PLATINUM(I) COMPLEX OBTAINED FROM THERMAL DEGRADATION OF PLATINUM(0)-TRIPHENYLPHOSPHINE COMPLEXES

Thermolysis of [Pt(PPh3)2(C2H4)], [Pt(PPh3)3] or of various complexes of the type [Pt(PPh3)2(alkyne)] in toluene gave the dinuclear platinum(I) complex [(Ph3P)Pt{µ-C6H4(PPh2)-2}(µ-PPh2)Pt(PPh3)] in ca. 60% yield as a consequence of both C–H and P–Ph cleavage of co-ordinated triphenylphosphine. The complex, which has been identified by mass spectrometry, NMR (31P, 195Pt) spectroscopy and single-crystal X-ray diffraction analysis, is probably identical with some of the compounds formulated in the literature either as [Pt2(PPh3)4] or [Pt2(µ-PPh2)2{C6H4(PPh2)-2}2]. The other product of the reaction is the known trinuclear compound [Pt3(µ-PPh2)3(Ph)(PPh3)2].

A Strategy for Identifying Novel Inhibitors of DNA Topoisomerase I

DNA topoisomerases alter DNA topology by transiently breaking either one (topoisomerase I) or both (topoisomerase II) strands of DNA (1). The essential role that these enzymes play in cellular processes such as DNA replication, transcription and recombination (2) suggests that they may constitute logical targets in the design of antineoplastic agents. In fact, several useful antitumor agents have now been shown to function, at least in part, via inhibition of DNA topoisomerase II (3,4).

Fresh routes to derivatives of cyclohepta[de]naphthalene

2,3-Dihydrocyclohepta[de]naphthalene-1,4-dione (1) is formed by cyclising methyl 3-(1-naphthoyl)propionate. It forms only monoacetals, gives a hemiacetal salt with alkali, and can be dehydrogenated to a quinone (14) that undergoes ring-contraction to a phenalenone (15) on acetalisation.Acenaphthylene traps dichloroketen inefficiently, allowing formation of the dimer (19) of tetrachloroallene, but dechlorination of the acenaphthylene adduct (16) followed by opening of its cyclobutanone ring with acid gives cyclohepta[de]naphthalen-2(1H)-one (21). This and the isomeric cyclohepta[de]naphthalen-1(2H)-one (23) obtainable from the dione (1), were reduced to alcohols with the object of preparing cyclohepta [de] naphthalene (26) by ester pyrolysis.

Quantitative aspects of Lewis acidity. Part XV. Basicity of substituted pyridines and quinolines towards metal halides in diethyl ether

BF3, GaCl3, SnCl4, ZnCl2, and PhSnCl3 form 1 : 1 adducts with substituted pyridines in diethyl ether solution. 1 : 1 Adducts are also usually formed with quinolines, but 2-substituted quinolines sometimes load to a 2 acid : 1 base species as the only observable adduct. Values of K1,1 for 1 : 1 adduct formation with pyridines follow the sequence BF3 SnCl4 > GaCl3 > ZnCl2 > PhSnCl3, and with quinolines the sequence BF3 > GaCl3 > ZnCl2. For ZnCl2 and unhindered quinolines the correlation equation pK1,1=–0.68pKa– 0.77 obtains. Compared with pyridines of comparable pKa values in water, quinolines are relatively weaker bases towards metal halides in diethyl ether. Both quinolines and pyridines are more basic towards metal halides in diethyl ether than are anilines of the same pKa value. The pKa values at 25° of 2-chloropyridine, 3,5-dichloropyridine, and 3-bromopyridine are 0.75, 0.70, and 2.85 respectively.