Catheduline alkaloids

As a result of a detailed collaborative investigation between the Chemistry Department of the University of Nottingham (Crombie, Whiting) and the U.N. Narcotics Laboratory (Szendrei), at least 14 cathedulin alkaloids have been isolated and formulated (46,47). Plant material collected in Kenya, Ethiopia, and the Yemen Arab Republic was extracted as fresh material, as freeze-dried material, and as sun-dried material. A number of extraction procedures were also employed, with methods directed toward the isolation of weak bases. In one procedure fresh material was extracted with ethanol in the presence of sodium bicarbonate, and the diluted extract was adjusted to pH 5.5 and extracted with... 

Two groups of the cathedulin alkaloids, E3, E4, E5, and E6 and Kl, K2, K6, and K15, form subsets which differ within each other only in the acetylated or nonacetylated state of certain hydroxyl groups. In consequence, certain alkaloids could be artifacts caused by deacetylation induced by isolation or chromatography, or acetyl migration might have unexpectedly occurred. This cannot be ruled out with certainty in all cases, but there is evidence which indicates in general... 

Little is known about the pharmacological activity of the cathedulin alkaloids. However, Kubo et al. (49) have reisolated cathedulins E3, E4, and E5 by HPLC and report that all three compounds are potent growth inhibitors for the pink bollworm at approximately 1 ppm. This is nearly as strong as azadirachtin, one of the strongest known natural growth inhibitors. 

The cathedulin alkaloids of medium molecular weight (750-9(K)) comprise four members, cathedulins Kl, K2, K6, and K15 with K2 (42) being the most intensively studied. It was shown by mass spectral and H- and C-NMR... 

VIII. Synthetic Work Relevant to Cathedulin Alkaloids... 

Sesquiterpenoid alkaloids similar to those of other celas-traceous plants occur in leaves of khat (Brenneisen and El-Sohly, 1992 Crombie, 1980) but do not appear to be responsible for the effect of chewing fresh khat (Szendrei, 1980). The active compound is a simple amine, cathinone (see Chapter 28). A series of complex sesquiterpenoid cathedulin alkaloids has been characterized from khat (Crombie et al., 1990). 

Although none of the known triterpene cores of the cathedulin group of alkaloids has been synthesized, progress has been made in the broader area of synthesis of Celastraceae sesquiterpenes, which is relevant to this problem. Thus, a completely stereoselective synthesis of the trihydroxylated dihydroagar-ofuran isocelorbicol (70) has been reported by Huffman and Raveendranath (60,61), which improves upon an earlier synthesis (62). The synthesis (Scheme 6) starts from the ketoagarofuran 71, which is available in six steps and 10% overall yield from carvone and methyl vinyl ketone. 

Khat, a drug produced from leaves and shoots of Catha edulis, is used as a stimulant, primarily in East Africa and Southern Arabia [167]. Interest in this drug led to investigation of the components of C. edulis, which included a number of macrocyclic sesquiterpene pyridine alkaloids, the cathedulins. 

KhaL Chat quat. Leaves of Caiha edulis Forsk, Celastraceae widely used in E. Africa and Yemen as an amphetamine-like stimulant. Most important consriruent is the alkaloid cathinone, q.v. also norpseudoephedrine, cathi-dine, cathedulin. lsoln and characterization of constituents of khat O. Wolfes, Arch. Pharm. 268, 81 (1930) H. Friebel, R, Bril la, Naturwiss. 50, 354 (1963) M. Cais el al. Tetrahedron 31, 2727 (1975) R. L. Baxter et al, Chem. Commun. 1976, 463. Pharmacology of khat extracts G. A. Alles et al, J. Med. Pharm. Chem, 3, 323 (1961). Reviews A. Geta-hun, A. D, Krikorian, Econ. Bot. 27, 353, 378 (1973) P, Kalix, Gen. Pharmacol. 15, 179 (1984). 

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