Daphniphyllum alkaloid

From Daphniphyllum macropodum, a group of alkaloids (164) with complicated structures has been isolated (131). This plant is large evergreen tree growing in the central to southwestern parts of Japan. Taxonomically this genus is classified in Euphorbiaceae but there is an argument that this genus should be treated as an independent family, Daphniphyllaceae. 

The main Daphniphyllum alkaloid is daphniphylline, the structure of which was clarified by X-ray crystallography (130). Several other alkaloids have been isolated, including secodaphhiphylline and yuzurimine. 

A careful inspection of the molecular structures suggested that the skeletal structure was derived from triterpenoids. Subsequent tracer experiments supported this view. 

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

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 ... 

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. 

In conclusion, the biosynthetic pathway from a squalene-like intermediate to the Daphniphyllum alkaloids must be acceptable (Schemes X, XI, and XIII) although the specific degradation studies have not been completed. 

Chapter 2. The Daphniphyllum Alkaloids Shosuke Yamamura and Yoshimasa Hirata... 

Tetracyclization. The Heathcock group1 has described a remarkably short and efficient synthesis of the skeleton of Daphniphyllum alkaloids (2) by reaction of the dialdehyde 1 with gaseous ammonia and then dissolution in acetic acid at 70°. The yield is 77%, based on the diol precursor to 1. The azadiene a and the imine b have both been isolated and identified. The conversion of a to b is an intramolecular Diels-Alder type reaction. The tetracyclization may well be involved in the biosynthesis of alkaloids such as Daphnilactone A (3). 

The limited reports of work on the Daphniphyllum alkaloids include the description of the isolation of two new compounds from D. humile. 

Yuzurimine C, a minor squalene-derived alkaloid from Daphniphyllum mac-ropodum,n has been assigned the structure (5). A search for further compounds to support the postulated biogenetic pathway from squalene to the Daphniphyllum alkaloids has resulted in the isolation of daphniteijsmanine (6) from D. teijsmanii.12 It is structurally very similar to secodaphniphylline. Treatment of the mesylate (8) of the sodium borohydride reduction product of N-acetylsecodaphniphylline (7) with acetic acid afforded N-acetyldaphniteijsmanine acetate (see Chapter 6, p. 214). Further chemical interrelations in this series have been described.13... 

The discovery395 of daphniteijsmanine (129) in Daphniphyllum teijsmanii supports previous suggestions that the Daphniphyllum alkaloids are formed from six molecules of MVA via a squalene-like intermediate (130). 

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