S. Morris Kupchan

Inhibition of Phosphofructokinase by Quinone Methide and α-Methylene Lactone Tumor Inhibitors

The plant-derived tumor inhibitors taxodone, taxodione, vernolepin, eupacunin, and euparotin acetate each inhibit the sulfhydryl enzyme, phosphofructokinase. The substrates, fructose-6-phosphate and adenosine triphosphate, protect the enzyme from this, inhibition as does the addition of dithiothreitol to the inhibitors. Incubation of taxodione with phosphofructokinase is associated with the loss of about one sulfhydryl group per inhibitor molecule, and the substrates protect six sulfhydryl groups per protomer of 93,000 daltons.

Calotropin, a Cytotoxic Principle Isolated from Asclepias curassavica L

An alcoholic extract of Asclepias curassavica L., a plant widely used in folk medicine for treating cancer and warts, shows cytotoxic activity when tested in vitro against cells derived from human carcinoma of the nasopharynx. Systematic fractionation of the extract has led to isolation and characterization of calotropin as a cytotoxic principle. Calotropin is similar in structure to two cardiac glycosides recently shown to be responsible for the cytotoxicity of Apocynum cannabinum L.

Beta-solamarine: tumor inhibitor isolated from Solanum dulcamara.

An alcoholic extract of Solanum dulcamara L., a plant widely used in folk medicine for treating cancers and warts, shows tumor-inhibitory activity against Sarcoma 180 in mice. Systematic fractionation of the extract has led to isolation and characterization of β-solamarine as an active principle.

Vernolepin: a new, reversible plant growth inhibitor.

Vernolepin (5 to 50 micrograms per milliliter), a novel sesquiterpenoid dilactone obtained from Vernonia hymenolepis, inhibits extension growth (from 20 to 80 percent) of wheat coleoptile sections. Inhibited tissues appear normal and their respiration is unaffected. If the inhibited sections are washed and subsequently treated with indole-3-acetic acid, the tissues respond to the auxin, but the degree of elongation is determined by the length of prior treatment with vernolepin. Administered simultaneously, increasing concentrations of auxin will significantly reduce the inhibitory effect of vernolepin, but there is no evidence for a competitive interaction between the two substances.

Hellebrigenin 3-Haloacetates: Potent Site-Directed Alkylators of Transport Adenosinetriphosphatase

Hellebrigenin, which diflers from strophanthidin only in its lactone ring, has 30 times the affinity of strophanthidin for the brain (Na + K)-activated adenosinetriphosphatase. Hellebrigenin 3-acetate and hellebrigenin 3,5-diacetate are about three times more potent toward this enzyme than hellebrigenin is. The 3-iodoacetate and 3-bromoacetate of hellebrigenin were synthesized and were highly potent irreversible inhibitors of the enzyme. The iodoacetate was 20 times more potent than the bromoacetate, as expected from the superior alkylating power of iodoacetate as compared to bromoacetate. The irreversible inhibition of the enzyme by hellebrigenin 3-bromoacetate and by strophanthidin 3-bromoacetate paralleled the affinities of the nonesterified steroids for reversible inhibition; this is further strong evidence for the site-directed alkylation of the (Na + K)-activated sinetriphosphatase by the haloacetate derivatives of the cardiotonic steroids.

A convenient separation of alkaloid mixtures by partition chromatography, using an indicator in the stationary phase

Abstract A convenient method has been developed for the separation of the alkaloids of Buxus sempervirens L. This method involves the use of partition chromatography on Kieselguhr, with an indicator in the stationary phase; the separate bands are detected visually, collected as a whole and in many cases crystallized directly. General considerations are presented concerned with the application of this method to other alkaloidal mixtures. The method is shown to give rapid and convenient separations of mixtures of bisbenzylisoquinoline alkaloids; of complex mixtures of indole alkaloids; and of mixtures of veratrum ester alkaloids, including an efficient and complete separation of a natural mixture of cevadine and veratridine.

Maytanprine and maytanbutine, new antileukaemic ansa macrolides from Maytenus buchananii

The structures of maytanprine (2) and maytanbutine (3), new antileukaemic ansa macrolides from Maytenus buchananii(Loes.) R. Wilczek, have been determined.

Novel photochemical aporphine synthesis via spirodienone rearrangement: (±)-boldine

The first synthesis of (±)-boldine (5), by photocyclization of the (±)-bromodiphenol (1) to the (±)-spirodienone (3), followed by rearrangement to (±)-N-ethoxycarbonylnorboldine (4) and reduction with LiAlH4, is reported.

Buxus alkaloids. VI. The constitution of Cyclovirobuxine-D

Abstract C-3 N C-20 N C-3 N C-20 N A CH 3 CH 3 CH 3 CH 3 F H H CH 3 CH 3 B CH 3 CH 3 H CH 3 G H CH 3 H H C H CH 3 CH 3 CH 3 H H H H CH 3 D H CH 3 H CH 3 I H H H H E CH 3 CH 3 H H On this basis cyclobuxine (I) (2) is renamed cyclobuxine-D, and cyclobuxamine (II) (3) is renamed cyclobuxamine-H.

Intramolecular catalysis. Facilitation of alkaline hydrolysis of alicyclic 1,2-diol monoesters

Abstract Evidence is presented for the view that alkaline hydrolysis of the ester grouping in cis alicyclic 1,2-diol monoacetates is facilitated by the adjacent hydroxyl group. Replacement of the hydroxyl group by methoxyl results in a substantial retardation in the hydrolysis rate. The mechanism of hydroxyl participation in the solvolysis of hydroxyacetates is discussed.