Daphniphyllum

Daphniphyllum spp. From the bark of D. macropodum Miq. Yagi isolated an amorphous alkaloid, daphnimacrine, m.p. 75-84°, which closely... 

Chorizanthe diffusa Dorstenia manni Daphniphyllum calycinum Moms cahayana... 

Scheme 2.154. Total synthesis of the Daphniphyllum alkaloid secodaphniphylline (2-692).

One very fascinating domino reaction is the fivefold anionic/pericydic sequence developed by Heathcockand coworkers for the total synthesis of alkaloids of the Daphniphyllum family [351], of which one example was presented in the Introduction. Another example is the synthesis of secodaphniphylline (2-692) [352]. As depicted in Scheme 2.154, a twofold condensation of methylamine with the dialdehyde 2-686 led to the formation of the dihydropyridinium ion 2-687 which underwent an intramolecular hetero- Diels-Alder reaction to give the unsaturated iminium ion 2-688. This cydized, providing carbocation 2-689. Subsequent 1,5-hydride shift afforded the iminium ion 2-690 which, upon aqueous work-up, is hydrolyzed to give the final product 2-691 in a remarkable yield of about 75 %. In a similar way, dihydrosqualene dialdehyde was transformed into the corresponding polycyclic compound [353]. 

Some pyranoindolizine-containing alkaloids have been isolated from plants of the genus Daphniphyllum. These are calyciphylline B, 292, an iV-oxide, and the two diastereomers, deoxycalyciphylline B, 293, and deoxyisocalyciphylline B, 294. Biosynthetic pathways for these molecules have been proposed however, little has been mentioned of any biological activity <2003OL2895, 2003JOC7961, 2005HCA854>. 

The chemistry of the Daphniphyllum alkaloids has been reviewed. Terpenoid alkaloids are also reviewed in the Specialist Periodical Report The Alkaloids . Two new alkaloids, deoxyyuzurimine (13) and isodaphnilactone B (14), have been isolated from the leaves of Daphniphyllum gracile ... 

Morita, H. Yoshida, N. Kobayashi, J. (1999) Daphnezomines C-E, new alkaloids with an AT-oxide moiety from Daphniphyllum humile. Tetrahedron, 55, 12549-56. 

Daphniphyllum is distributed through eastern Asia from China south through Malaysia to tropical Australia. Some species are used as ornamentals the Ainu of Japan use the leaves of one species as tobacco. 

Two new alkaloids from Daphniphyllum gracile Gage have been reported.2 Plants of the related species Daphniphyllum humile Maxim have been implicated in cattle poisonings in Hokkaido, Japan.3... 

Daphniphyllidine has been cited as the alkaloid D isolated from the bark and leaves of the plant Daphniphyllum macropodum Miquel [see Toda et al. (14)]. 

The carbon skeletons of the Daphniphyllum alkaloids consist of thirty or twenty-two carbon atoms. Probably the C22 alkaloids are formed by oxidative cleavage of eight carbon atoms from the C30 compounds. Methyl homodaphniphyllate [23, m/e 359(M+), 286, and 272], one of the representative C22 alkaloids, was isolated from the fruits of D. macropodum (19) but not from the bark and leaves of the same plant. The structure of this alkaloid (23) was deduced by chemical transformation from daphniphylline (1) which had already been carried out in several steps. Oxidation of deacetyldaphniphylline (2) with NaI04 followed by reduction with NBH afforded daphnialcohol [24, mp 239-241.5° (as hydrochloride) C21H350N], which was further converted via the corresponding tosylate (25, mp 107.5°) and nitrile (26, mp 156°) to homodaphniphyllic acid (27), which was directly treated with 20% methanolic HC1 to afford methyl homodaphniphyllate (23). This alkaloid was also obtained in 20% yield by Beckmann... 

A list of the Daphniphyllum alkaloids is given in Table I. In addition to two alkaloids of undetermined structure, neodaphniphylline (28) and neoyuzurimine, both of which have been isolated in very small quantities (Vol. X, p. 556, and Vol. XII, p. 472), three more structurally unknown alkaloids (alkaloids Ax and A2, and yuzurimine-D) have been obtained from the bark and leaves of D. macropodum (14, 21). In particular, the carbon skeletons of the alkaloids Aj and A2 seem to be considerably different from those of the other alkaloids cited in parts A-E, on the basis of their spectral data. 

Scheme VIII. Structural relationships among the Daphniphyllum Alkaloids.

Daphniphyllum macropodum contains a great variety of related alkaloids whose structures are quite complex and novel (Section II). It is structurally evident that these alkaloids with an isopropyl or a potential isopropyl group are regarded as a terpene alkaloid. Bio-genetieally, these Daphniphyllum alkaloids, particularly C22 alkaloids, have been proposed to be derived from four molecules of mevalonic acid (MVA) and one acetate unit (15, 39). However, the recent tracer experiments showed that these alkaloids could be biosynthesized from six MVA molecules through a squalene-like intermediate. Accordingly, they should be included in a group of triterpene alkaloid. 

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