Broussonetines

Biosynthetic studies were conducted on broussonetine J 13, which was isolated from 50% methanol extracts of plantlets fed with [l- C]glucose. However, the H- and C-NMR spectra of 13 were too complicated to analyze, suggesting the presence of rotational isomers of the two amide moieties. Therefore, compound 

FIVE-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

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M. Shibano, S. Kitagawa, and G. Kusano, Studies on the constituents of Broussonetia species. I. Two new pyrrolidine alkaloids, broussonetines C and D, as (l-galactosidasc and P-mannosidase inhibitors from Broussonetia kazinoki SIEB., Chem. Pharm. Bull., 45 (1997) 505-508. 

The bioactive secondary metabolites reported from Broussonetia kazinoki can be classified into major two groups, alkaloids and flavonoids (Table 1), Fig. (1). The Kusano group at Osaka University of Pharmaceutical Sciences in Japan reported over 20 pyrrolidine alkaloids, broussonetines A-H, K-M, O-T, V-X, and Mi, and broussonetinines A and B, four pyrrolidinyl piperidine alkaloids, broussonetines I, J, Ji, and J2, two pyrroline alkaloids, broussonetines U and U, and one pyrrolizidine alkaloid, broussonetine N, from hot water extracts of B. kazinoki [16-24]. As shown in Table 1, some of these alkaloids exhibited strong... 

The relative stereochemistry of the pyrrolidine ring of broussonetine C (1) was determined from its coupling constants (vicinal coupling, 2,3 = = Ja = 6.4 Hz) and nuclear Overhauser enhancement... 

Fig. (2). Determination of the absolute stereostructure of broussonetine C (1) by the benzoate chirality method.

The absolute stereochemistry of broussonetine L (8) was determined by the combination of the benzoate chirality method and the Mosher s method [35-37]. A carbamate (8a) was prepared from broussonetine F (4) by reaction with phenyl chloroformate in tetrahydrofuran-H20 (7 3), and a diacetate (8b) was prepared from 8a with acetic anhydride in pyridine. Finally, a dibenzoate (8c) was obtained by benzoylation of 8b. The CD curve of 8c showed a negative Cotton effect (Ae237 -30.9) and a positive effect (Ae223 +15.9) to confirm a counter-clockwise chirality between two benzoyl groups, Fig. (3) [20]. 

A biosynthetic study of the 18-carbon chain skeleton of broussonetines was reported [38]. To verify the biosynthetic route of these alkaloids, the plant was grown on an aseptic medium and the enriched l3C of the isolated alkaloids was analyzed by NMR after feeding with [l-13C]glucose. The labeling pattern of broussonetine J (27) obtained... 

Fig. (5). Determination of the absolute configuration of broussonetine N (15) by the Mosher s method.

Only three constituents have been reported from Broussonetia zeylanica, all by a group at the University of Peradeniya in Sri Lanka [89-91]. A major alkaloid, 8-hydroxyquinoline-4-carbaldehyde (55), was identified as an antimicrobial agent active against Staphyllococus aureus and Candida albicans (the levels of activity were not specified) [89] and then two minor compounds, 3,4 -dihydroxy-2,3 -bipyridine (56) and 3,4-bis(8-hydroxyquinolin-4-yl)-y-butyrolactone (broussonetine, 57), were reported, Fig. (10) [90,91]. However, the structure of 3,4 -dihydroxy-2,3 -bipyridine (56) was revised to 8-hydroxyquinoline-4-carbaldehyde oxime (58) by synthesis [92,93]. Also, it was noted that an artefactual origin of this oxime (58) could not be ruled out due to the presence of the corresponding aldehyde (55) [93]. 

R, 3R, 5S, 8/ )-l,2-dihydroxy-3-hydroxymethyl-5-[(l/ )-l, 10-dihydroxy-6-oxo-decyl]-pyrrolizidine (Broussonetine N) Broussonetia kazinoki (Moraceae) branches ... 

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