Yuzurimine daphniphyllum

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. 

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... 

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 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. 

Of 10 structurally known alkaloids belonging to the yuzurimine group, deox-yyuzurimine [36 mp 132-124°C C27H37O6N m/z 471 (M )] (Fig. 5) was isolated as a minor component from the species Daphniphyllum humile (7). The spectral data of 26 were completely identical to those of the reduction product obtained from yuzurimine (5) on zinc reduction in acetic acid (90-95°C, 2 hr). 

Further, the mutagenic activity of five daphniphyllum alkaloids (codaph-niphylline, daphnilactone-B, yuzurimine, yuzurimine-C, and deoxyyuzurimine) was examined by Hashimoto and Ushijima (79), using Salmonella typhimurium variant TA 100 and TA 98. However, none of them were found to show any mutagenic activity. 

Calyciphylline A-type alkaloids are a group of rare C-22 fiised hexacyclic nor-Daphniphyllum alkaloids, biosynthesized by the fission of C-l-N bond of yuzurimine-type alkaloid and the formation of a new bond between C-4 and nitrogen. Calyciphylline A-type alkaloids possess a 6/5/5/7/5/6-membered ring system and an oxo group on C-1. 

Calyciphylline B type alkaloids are a group of rare C22 fused-pentacyclie yuzurimine type nor-Daphniphyllum alkaloids. Most of them eontain a six-member laetone ring. A new ealyciphylline B type alkaloid, daphlongamines H (51) was reported (Figure 13) [45]. 

Coldham et al. reported on a cascade reaction sequences involving condensation, cyclization, intramolecular dipolar cycloaddition for preparation of fused tricyclic heterocycles which can be converted in two steps to a 1,3-oxazine present in some yuzurimine-type Daphniphyllum alkaloids under some conditions [57], In another study, addition of hydroxylamine to substituted 4-chlorobutanals gives intermediate nitrones that imdergo tandem cyclization and then intramolecular dipolar cycloaddition to give the core... 

Coldham, L. Watson, H. Adams, N. G. Martin, Synthesis of the core ring system of the yuzurimine-type Daphniphyllum alkaloids by cascade condensation, cyclization, cycloaddition chemistry, J. Org. Chem. 76 (2011) 2360-2366. 

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. 

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