Yuzurimine alkaloids

Numerous UCNMR investigations on alkaloids have been reported in the literature [598, 599]. In Table 5.13 the 13C chemical shifts and structures of representative alkaloids of different types are collected Pyrrolidine, piperidine and pyridine [600-602], tropane [600, 603-605], izidine [606-612], indole [600, 603, 613-633], isoquinoline [599, 630, 634-647], quinolinic [648-656], imidazole [657], yuzurimine alkaloids [658], alkaloids with exocyclic nitrogen [659, 660], diterpenoid [661-663], steroid [664-666] and peptide alkaloids [667-671], The complete signal assignment for the alkaloids given in Table 5.13 was achieved using the correlations between 13C NMR spectral parameters and structural properties and the 13C chemical shift values of model compounds described in Chapters 3 and 4 of this monograph. 

From a structural viewpoint, these alkaloids are mainly divided into five types of nitrogen heterocyclic skeletons represented by daphniphylline (I), secodaphniphylline (28), daphnilactone-A (34), daphnil-actone-B (36), and yuzurimine (43). In this chapter, all of these alkaloids will be described including their spectral and chemical properties. Biogenesis of these bases with complex structure is quite interesting... 

Biogenetically, daphnilactone-B (36) is regarded as a plausible intermediate between daphniphylline-type and yuzurimine-type alkaloids. Thus, daphnilactone-B (36) was converted to a daphniphylline-type compound (38, mp 166-168° C22H3302N) via a bromocyanamide [39, mp (dec) 210°] and a debromocyanamide (40, mp 208-212°), as shown in Scheme V. The structure of this daphniphylline-type compound 38 was confirmed by its mass, IR, and NMR spectra coupled with von Braun degradation of 38 leading to the formation of a new... 

Yuzurimine [43 [a]D + 8.3° (in CHClg)] is one of the major alkaloids isolated from the bark and leaves of D. macropodum. The spectral data... 

Yuzurimine-B (52) is a minor alkaloid crystallized as the hydrochloride which has a secondary methyl group [81.22 (3H, d, J = 6.0... 

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. 

As reported by Yagi (3) a small amount of yuzurimine (43) acts as a weak depressant for the central nervous system. With larger quantities it was proved that this alkaloid had an efficient effect on muscle relaxation and sedation. 

The Alkaloids of Daphniphyllum humile Deoxy-yuzurimine and Isodaphnilact-one-B.-Yamamura and Terada55 have isolated two new alkaloids from the leaves of D. humile M. Deoxy-yuzurimine (150), C27H37NO6, m.pt. 132 °C, was found to be identical with the previously reported product56 of the reduction of yuzurimine... 

Alkaloids of Daphniphyllum humile Deoxy-yuzurimine and Isodaphnilactone-B 243... 

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... 

In 1966, Hirata et al. isolated yuzurimine (12) as one of the major alkaloids from D. macropodum and reported the crystal structure of yuzurimine hydrobromide [25]. They also isolated the two related alkaloids yuzurimines A (13) and B (14), whose structures were elucidated through spectroscopic data and chemical evidence in 1972. At almost the same time, Nakano et al. isolated macrodaphniphyllamine (16), macrodaphniphyllidine (17), and macrodaphnine (18) [15,29], whose structures were identical with deacetyl yuzurimine A, acetyl yuzurimine B, and dihydroyuzurimine, respectively. Yamamura et al. isolated deoxyyuzurimine (19) from D. humile [30], and daphnijsmine (20) and deacetyl daphnijsmine (21) from the seeds of D. teijsmanni [23]. Calycinine A (22) was isolated from D. calycinum distributed in China, together with deacetyl daphnijsmine, deacetyl yuzurimine, and the zwitterionic alkaloid 26 [31] (Figure 18.3). 

Daphnezomines C (39) and D (40), possess the secodaphniphylline-type skeleton with a nitrone functionality, while daphnezomine E (41) is the first N-oxide of a daphniphylline-type alkaloid, though the N-oxides of several yuzurimine-type alkaloids have been reported [45]. 

The structures, including relative stereochemistry, of daphnezomines H (44), I (4S), J (46), and K (47), four new alkaloids possessing a daphnilactone-type (44 and 4S) or a yuzurimine-type skeleton (46 and 47) were elucidated on the basis of spectroscopic data [47]. Daphnezomine I is the first N-oxide alkaloid having a daphnilactone-type skeleton, while daphnezomine J is the first alkaloid possessing a yuzurimine-type skeleton with an anti-Bredt-rule imine [57,58]. 

A. Structure.— The plant Daphniphyllum macropodwn Miq. contains a great variety of related alkaloids (see Table). Three main N-heterocyclic skeletons occur, represented by daphniphylline (152), secodaphniphylline (156), and yuzuri-mine (157). Within the daphniphylline group, notable variations in the oxygen heterocycle occur in daphmacrine (154) and daphnimacropine (155). Macrodaph-nine (161) is the A-oxide of yuzurimine. The structures of representative members... 

The structure of yuzurimine (XLVII) had already been shown to be of a different type from that of daphniphylline and the isolation of two more alkaloids was reported (73). Yuzurimine A, C25H35O5N (hydrochloride, mp 249°-252°), was shown to be desacetoxyyuzurimine (XLVIII) by... 

Daphnijsiiiine and Desacetyldaphnijsmine.—These alkaloids, C25H33NOS, m.p. 205—207 °C, and C23H31NO4, m.p. 200 °C, contain amine oxide functionalities. From spectral data and biogenetic considerations, structures (80a) and (80b), respectively, were assigned.These alkaloids may be classified in the yuzurimine group. The or/8,y5-unsaturated methoxycarbonyl system suggests that they may have been derived from a precursor (81) related to daphnilactone-B. ... 

The structure of yuzurine was determined to be (88) by an X-ray crystallographic study of the methiodide derivative, employing a heavy-atom method. This structure accounts for the observed chemical and physical data. The proposed biosynthetic pathway from yuzurimine-B (89) is indicated in Scheme 2. Yuzurine, which may be included in the yuzurimine class, differs from the previously isolated Daphniphyllum alkaloids in that it has no 2-azabicyclo-[3,3,l]nonane system. 

X-ray crystallographic determination utilizing direct phasing methods. Although this compound contains the 2-azabicyclo[3,3,l]nonane ring system common to all of the Daphniphyllum alkaloids, it represents another new structural type. It is possibly related to yuzurimine (61) by formation of a C-8—C-22 bond and double-bond migration from C-8—C-9 to C-8—C-12. 

From a structural point of view, the 38 alkaloids so far obtained from the Daphniphyllaceae are classified into six types of nitrogen heterocyclic skeleton represented by daphniphylline (1), secodaphniphylline (2), daphnilactone-A (3), daphnilactone-B (4), yuzurimine (5), and daphnigracine (6), as shown in Fig. 1. Of the alkaloids, the 9 daphnigracine-type alkaloids are distinct from the other types in the following point they have no 2-azabicyclo[3.3. l]nonane ring system in their structure. 

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