Hernandia isolates from

The following secodimeric alkaloids have been isolated from natural sources (+)-hernandaline (197), from Hernandia ovigera L. (158), (—)-natalinine (198) (759), and (+)-coyhaiquine (199) (160), the two latter from Berberis empetrifolia Lam. with the yields 0.00005 and 0.00008%, respectively. Appropriate aporphine-benzylisoquinoline or proaporphine-benzylisoqui-noline dimers are probably precursors of these seco alkaloids, although... 

Efatine (465), CjgH NjOg, amorphous, [a]D +70° (c 0.86, CDC13), isomeric with ambrimine (464), was also isolated from Hernandia peltata. The substitution patterns of ring C in efatine and 464 could be distinguished by NOE measurements and by NMR base shift with NaOMe/DMSO-d6 (549,550). 

The noraporphine nandigerine, C18H17O4N, was isolated from Hernandia ovigera L. (Hernandiaceae). The base crystallized from methanol either as solvent free needles (mp 176°-177° [ajp - -248° in ethanol), or as plates of the methanol solvate, C]8Hi704N-CH30H (mp 99°-100°). The alkaloid hydrochloride salt melted at 245°-247° (decomp.) (33b). 

Thalicarpine (LX), C41H48O8N2 (mp 160°-161°) was first isolated from Thalictrum dasycarpum Fisch. and Lall. (30). Later it was obtained from Thalictrum minus L. var. datum Jacq. (31) and from Hernandia ovigera (Auth. ) (32). 

The two Type Vb alkaloids are both of the S,S stereochemistry and have the same linkage as the Va alkaloids, but the former have extra oxygenation at C(ll). Ambrimine (272) and efatine (296) are monophenolic in Ring C and have only been isolated from Hernandia nymphaeifolia (Hemandiaceae). 

Hata first isolated desoxypodophyllotoxin, which showed mp 167- -168t) and [a ]D -116° (c=2 in CHC1,), from the seeds of Hernandia ovigera, and he named it "hernandion". However this compound was identical with anthricin which was isolated from Anthricus sylvestris Hoffm. (ref. 6). Subsequently it was found to be identical with a product resulting from dehydroxylation of podophyllotoxin (11) by Hartwell and co-workers (ref. 7). Since this compound has been given several names, it is reasonable to call it "desoxypodophyllotoxin" on account of the structural relationship with podophyllotoxin according to Hartwell s proposal (ref. 8). 

Hernolactone (16) is a new bisbenzyl- y -butyrolactone-type lignan isolated from Hernandia ovigera. Although the syntheses of bisbenzyl- y -butyrolactones have been reported by many groups (ref. 2), its synthesis was carried out according to the known procedure (ref. 35) shown in Chart 6. 

Table 3. Cytotoxic Effects of Isolates from Hernandia Species Against Selected Human and Murine Cancer Cell Lines b...

Tetradecanoylphorbol 13-acetate (TPA) and other diterpene esters from the plant family Euphorbiaceae are well-known as tumor-promotion agents [85]. Thus, inhibition of the biological effects induced by TPA has been considered as a promising strategy [68]. To date, two short-term cell-based in vitro bioassays using TPA as a tumor-promoter have been developed to evaluate the potential cancer chemopreventive activities of several lignans isolated from Hernandia species, namely, inhibition of Epstein-Barr virus early antigen activation [6] and the inhibition of the transformation of JB6 mouse epidermal cells [7]. 

Table 4. Inhibitory Effects of Isolates From Hernandia Species on the Induced Aggregation of Washed Rabbit Platelets b...

It has also been isolated from Thalictrum minus Linn., Thalictrum revoluctum and Hernandia ovigera (Family Hernandiaceae). 

Oxoaporphines.—Recent sources for known oxoaporphines are liriodenine, Melodorum punctulatum (Annonaceae) 0-methylatheroline and cassamedine, Annona purpurea L. (Annonaceae) and dicentrinone, Ocotea macropoda (Lauraceae). New oxoaporphines are oxopurpureine (122), isolated from Annona purpurea L., and hernandonine (123) found in Hernandia ovigera and H. jamaicensis (Hernandiaceae). ... 

Isol. from seed oil of Hernandia ovigera. Lignan of deoxypodophyllotoxin type. 

Only three iw-aporphine alkaloids (V.1-V.3) were isolated from the two Hernandia species found in Taiwan, the trunk bark of H. nymphaeifolia (Presl.) Kubitzki (25,34) and the root bark of H. ovigera L. (35,36). Two of them [ovihemangerine (V.2) and oviisocorydine (V.3)], possess cytotoxic activity in vitro against human colon cancer cell lines (25) (Table II). (+ )-Ovigeridimerine (V.l), at 50.0 pM, does not inhibit in vitro the platelet aggregation induced by arachidonic acid, collagen, and PAF (13) and the vasorelaxing effect caused by and norepinephrine (22). 

Five isoquinoline alkaloid dimers with pavine and tetrahydrobenzylisoquinoline moieties, known as hervelines A-D (VIII.1-VIII.4) and HB (VIII.5), have been isolated from the stem bark of Hernandia voyronii Jum. (8,9,48), used as an adjuvant to chloroquine in Malagasy herbal practice and against chronic malaria (8,9). Two of them, harvelines B (VIII.2) and C (VIII.3) reversed in vitro chloroquine resistance to the resistant strain of P. falciparum (9) and exhibited moderate antimalarial activity (8,9,48). Harveline HB (VIII.5), an alkaloid whose structure has not been determined, also potentiated the effect of chloroquine and showed weak in vitro cytotoxicity against HeLa cells (48). 

A few alkaloids with pyridine (XIII), proaporphine (XIV), and phenanthrene (XVI) nuclei were also found in the Hernandia, Gyrocarpus, and Illigera species, respectively (Table I). Phenanthrene alkaloids, also known as seco-aporphines, are a very rare type, probably formed biogenetically from an aporphine precursor through the opening of ring B (28). Castedo and Tojo have reviewed their chemistry (50). From the family Hernandiaceae only thaliporphinemethine (XVI.l) was isolated from I. pentaphylla Welw. (51). 

Thalicarpine was isolated from Cocculus laurifolius (73) in 1982. It is one of the rare examples of a tetrahydrobenzylisoquinoline-aporphine dimer. Thalicarpine seems to originate biogenetically from the oxidative coupling of two molecules of reticuline forming initially a Bis-BIQ. A second oxidative coupling, this one intramolecular, leads to the final product (Scheme 22). This alkaloid was also isolated from Thalictrum spp. (Ranunculaceae) and Hernandia ovigera (Hemandiaceae). 

Although earlier described from 3-year-old Thalictrum minus extracts as a probable artifact of air oxidation (555) of thalmelatine (314a), 6a,7-dehydrothalmelatine (474), C A, was only recently isolated as a natural product from Hernandia peltata. Identification was by comparison of spectral data with published values (549). 

The plants of Hernandiaceae comprise about sixty-five species in four generic kinds. The plants of Hernandia ovigera L. are widespread in the tropics and the subtropics. In Japan, these plants grow on the beaches of Okinawa and Ogasawara islands. In the Okinawa region, the plants have been used as therapeutic agents. A number of groups have been involved in the isolation and structure elucidation of aporphine-type and isoquinoline-type alkaloids from these plant materials as well... 

Extraction and Isolation of the Lignans from the Seeds of Hernandia ovigera... 

The first example of a naturally occurring isoquinolone was doryanine isolated by Gharbo.et al. (1965) from the Australian sassafras tree Doryphora sassafras, and workers of the same laboratory later isolated doryphomine from the same species (Chen et al. 1974). The authors assumed that isoquinolones may be formed in the plant by oxidation of benzylisoquinolines or similar alkaloids, and this view now appears to be generally accepted (Krane and Shamma 1982). Indirect support for this hypothesis may be the presence of the bisbenzyhsoquinoline alkaloid thali-carpine and its two oxidation products hemandaline and N-methyl-6,7-dimethoxy-l-isoquinolone in Hernandia ovigera (Cava and Bessho 1966). 

Canonica L, Galliani G, Lesma G, Tollari S (1981) Enzymatic transformations of alkaloids utilizing pure enzymes. Proc 1st Int Conf Chem Biotechnol Biol Act Nat Prod Istvol. 2 522-527 Cava MP, Bessho K (1966) Hernandia alkaloids II. Hernandaline, a new elaborated aporphine structural type. Tetrahedron Lett 36 4279-4282 Chen CR, Beal JL, Doskotch RW, Mitscher LA, Svoboda GH (1974) A phytochemical study of Doryphora sassafras II. Isolation of eleven crystalline alkaloids from the bark. Lloydia 37 493-500... 

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