Tetrahedron. Vol. 30, pp. 2461 lo 2466. Pergamon Press 1974. Prlnled in Gre.l Brilain CYCLOPEPTIDE ALKALOIDS OF ZIZYPHUS OENOPLIA 1 B. K. CASSELS: G. ECKHARDT,B.-U. KAUSSMANNand R. TSCHESCHE* Institut für OrganischeChemieund Biochemieder UniversitiitBonn, D-53Bonn,Germany (Received in the UK 14 December 1973; Acceptedforpublication 20 February 1974) Abstract-The known alkaloids zizyphine-A (1) and -B (2), abyssinine-A (4) and -B (5), and the previously undescribed zizyphine-C (3), -D (6) and -E (7) have been isolated from the stem bark of Zizyphus oenoplia. The structures of the new compounds were elucidated by spectroscopic methods applied to the alkaloids and to some of their transformation products, and by chemical degradation reactions. While working up the crude bases obtained from the stem bark of Zizyphus oenoplia MilI. t for a revision of the structure of zizyphine-A (1)/ the mixture was found to contain, besides this substance and the previously described zizyphine-B (zizyphinine) (2),2,3 several other alkaloids, some of which are now reported. Extensive chromatography of the crude bases furnished eight apparentIy homogeneous frac- tions (Table 1), one of which was subsequentIy shown to be composed of two substances separable only by chemical means. Of these nine alkaloids, the structures of four are already known: zizyphine-A and -B, and abyssinine-A (4) and -B (5).' Two of the so far undescribed substances were present in insufficient amounts for structural work to be carried out. Of the remaining three, one, zizyphine- C (3) was found to contain a 13-membered ring like zizyphine- A and -B. The other two new compounds, zizyphine-D (6) and -E (7), have 15-membered rings like abyssinine-A and -B, with the peculiarity that one of the amino acids is 3-hydroxy-isoleucine. Zizyphine-C (3). The mass spectrum of this • FeIlowof the Alexandervon Humboldt-Stiftungduring 1973. Present address: Laboratorio Central de Química, Universidad Técnica del Estado, Santiago, Chile. tCoIlected in India by Prachi Gobeson, Calcutta. alkaloid, which shows a molecular ion peak at m/ e 645 and an intense base peak at m/e 148, closely resembles the spectrum of zizyphine-A, with most of the peaks displaced 34 mass units upwards, sug- gesting that zizyphine-C is an analog of zizyphine-A with the terminal N,N-dimethyl-isoleucine moiety replaced by an N ,N-dimethylphenylalanine residue. The IR spectrum display s characteristic secon- dary amide bands as well as absorption attributable to a conjugated, cis-l,2-disubstituted C=C double bond, an aryl ether, methoxy and N-Me groups. The UV spectrum shows that a fairly flat styrylamine chromophore is present, as in the cases of zizyphine- A and -B, mucronine-D: and amphibine-H.5 The PMR spectrum confirms the presence of an N,N-dimethyl group, a OMe group and a cis- styrylamine moiety. Two NH signals are recogniza- ble, one of them partly obscured by the large singlet due to phenyl protons. As in the cases of zizyphine-A and amphibines-B, -C, -D and -E; the coupling (J = 6 Hz) between the protons at C-2 and C-3 of the 3-hydroxyproline unit (8 4·33 and 5·24, respectively) indicates that the dihedral angle be- tween them is probably in the ranges 45-55° or 130-140°.7 Oxidative cleavage of the styrene double bond with OsO./NaIO. yielded a single product which was Table 1. Chromatographically hornogeneous alkaloidal fractions from Zizyphus oenoplia Mili Percentage of Fraction crude alkaloids Composition M+ Base peak 52·5 zizyphine-A 611 114 7·6 zizyphine-B and -C (l : 2) 597,645 100,148 7·6 zizyphine-D 474 72 4·9 abyssinine-B 458 163 4·0 zizyphine-E 460 72 1·5 701 114 0·8 abyssinine-A 458 163 0·6 486 72 2461