Hasubanonine alkaloids

The first synthesis of hasubanonine (33) and a second of the related alkaloid cepharamine (34) (via the newly developed enamine annelation approach) were accomplished. Two new hasubanonine alkaloids, stephisoferuline (35) and stephavanine (36)were isolated from Stephania hemandifolia and S. abyssniea. respectively. Stephavanine is the most highly oxygenated hasubanonine alkaloid Isolated to date. 

Mass Spectral Data for Hasubanan Alkaloids of Hasubanonine-Type Cleavage... 

Table VII gives a survey of alkaloids that exhibit the hasubanonine-type cleavage. The characteristic fragmentation pattern of this group, possessing an a,/ -unsaturated carbonyl group in ring C, is significantly different from other groups. In the case of hasubanonine (5) (3), the most abundant and nitrogen-free ion peak was observed at m/z 315, which is important for structure elucidation of this group (2,73).

During the period 1976-1986, biosynthetic studies on hasubanan alkaloids were carried out by Battersby et al. (81-84) for hasubanonine (5) together with protostephanine (57). The two alkaloids, isolated from Stephania japonica, arise from the same precursor, and their unusual structures are of biosynthetic interest, namely, the vicinally trioxygenated ring C in 5 and the unique natural example of a dibenz d,f ] azonine skeleton in 57. 

Morphine alkaloids are a subgroup of isoquinoline alkaloids and are derived biogenetically from laudanosine bases by oxidative phenolic coupling/6,7 Alkaloids of the opposite enantiomorphic group occur in several Japanese Sinomenium and Stephania species, the most important compounds being sinomenine, hasubanonine, metaphenin, and protometaphenine. 

In an investigation of the point of attachment of the nitrogen in the alkaloid hasubanonine from Stephania japonica, the base 254 was prepared from 14-bromocodeinone.<384)... 

Sinomenine, discovered by Ishiwari in Smomenium diversifolius [97], has been shown by the researches of Kondo [98] and particularly of Goto and his co-workers [99-100] to have the structure [nxvn] and to be the optical antipode of 7-methoxythebainone. It is readily converted into antipodes of substances obtainable from thebaine and codeine (see Chap. XXVI). Hasubanonine, an alkaloid isolated from Stephania japonica, is believed to be of the morphine type [101] (see Chap. XXVI). 

Hasubanonine could therefore have the structure [cxvi] which could suffer loss of the 6-methoxyl group during the Hofmann degradation to give the methine [cxvn] the structure [cxvm] for the methine is untenable as acetolysis, hydrolysis, and methylation of this would give dimethylsinomenol. Alternatively hasubanonine could be [cxix] and the methine [cxx]. Further speculations, however, are pointless until the chemistry of the alkaloid has been more fully investigated. 

A new alkaloid, hasubanonine, believed to be of the morphine type has recently been isolated and studied. It can be degraded to a methine base, the acetolysis of which gives a trimethoxyacetoxyphenanthrene, which has been converted to the corresponding trimethoxyhydroxy- and tetramethoxyphenanthrenes. The structure of these compounds is not yet known [117], but the properties of the tetramethoxyphenanthrene differ from those of dimethylsinomenol [xcvn]. 

Thornber compared the presence of 11 benzylisoquinoline alkaloids in the plants of the Papaveraceae, Menispermaceae, Berberidaceae, Magnol-iaceae, Ranunculaceae, Tutaceae, Monimiaceae, Annonaceae, Aristolo-chiaceae, Lauraceae, and Nymphaceae, and he concluded that the alkaloids cularine and morphine (including codeine and thebaine) are present only in the genera Corydalis and Dicentra (alkaloid cularine) and in the genus Papaver (morphinane alkaloids) the hasubanonine and bisben-zylisoquinoline alkaloids do not occur in Papaver plants (838). 

Hasubanan alkaloMa. H. a. are a subgroup of the morphinan alkaloids occurring only in Stepkania species (Menispermaceae), e. g. hasubanonine. 

Hasubanonine-like alkaloids are known from the genera Sinomenium and Stephania (Menispermaceae). A biogenetic pathway leading to the formation of hasubanonine (55) and protostephanine (56) has been proposed (Battersby et al., 1974, 1977, 1981a, 1981b, 1981c) (Fig. 32.19). In experiments in which labeled precursors were fed into whole plants, Battersby and co-workers found that simple tyramine derivatives such as 2-(3,4-dihydroxy-5-methoxyphenyl)eth-... 

Battersby, A. R., R. C. F. Jones, R. Kazlauskas, A. P. Ottridge, C. PouPAT, and J. Staunton, Biosynthesis. Part 23. Degradative studies on the alkaloids hasubanonine and protostephanine from Stephania japonica, J. Chem. Soc. Perkin Trans. I, 2010-2015 (1981b). 

Castle and co-workers used a ring-closing metathesis strategy in their synthesis of the carbocyclic core of ( )-hasubanonine, a member of the hasubanan alkaloid family." Hasubanan alkaloids are of interest due to their structural similarity to morphine alkaloids. Treatment of diene 220 with a catalytic amount of 4 in refluxing dichloromethane furnished the desired phenanthrene core 221 in quantitative yield. Six additional steps were required to obtain the desired natural product. 

---