Hasubanane alkaloids

The hasubanan alkaloids had been discussed as a subgroup of morphine alkaloids in Volume 13 of this treatise (/) until the succeeding review was published in 1977 (2) the two reviews cover the literature up to 1976. Since the... 

Table I gives a survey of the occurrence and physical constants of the hasubanan alkaloids, including the congeners offered in the previous review (2).

Table II presents H-NMR data of the hasubanan alkaloids obtained since 1976. During the period 1976-1986, the application of H-NMR spectroscopy was accelerated together with the improvement of measuring instruments. NOE, INDOR, and two-dimensional NMR experiments (7) have been undertaken to resolve the question of stereochemistry at the chiral centers.

A major study on 13C-NMR spectroscopy of hasubanan alkaloids was carried out by Matsui et al. (5) (Table III). They proposed assignments of all carbon atoms including the direct and long-range hetero coupling. The C-9 and JV-methyl carbons of hasubanan alkaloids reveal shifts of 6 and 20 ppm higher frequency than those reported for morphinan alkaloids (9). On the other hand, the iV-methyl carbons of hasubanans exhibit a lower frequency shift of 10 ppm relative to those of hasubanalactam-type alkaloids (5). These results have been utilized for structure elucidation in later works (4,7,10-12). 

The structural features of this group are summarized as follows (1) possession of an acetal or a hemiacetal ether linkage between C-8 and C-10, and (2) either absence of a substituent or presence of a hydroxyl group or ester moiety at C-6. Because a large number of hasubanan alkaloids follow this cleavage pattern, the metaphanine-type cleavage may be one of the primary pattern for all hasubanan alkaloids (76). 

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

During a search for physiologically active compounds in South African plants, a new hasubanan ester acetal alkaloid, methylstephavanine (6), was isolated from Stephania abyssinica (19). The H-NMR spectrum of the new alkaloid 6 exhibited signals for one methylenedioxy, one N-methyl, and four methoxyl groups (19) (Table II). Its mass spectrum revealed the most abundant ion peak at m/z 229, indicating a close resemblance to the known hasubanan alkaloid, stephavanine (18). 

Finally, the structure of oxostephasunoline (4) was confirmed by the following chemical correlation with several known hasubanan alkaloids. Heating the new alkaloid 4 in an ethanolic hydroxide solution gave 16-oxoprometaphanine (33), which on treatment with dilute hydrochloric acid yielded 16-oxometaphanine (33). Thus structure 4 was proposed for oxostephasunoline (4). As stated in Section I, the hasubanan alkaloids carrying a... 

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. 

Four synthetic hasubanan alkaloids, 3,9/ -dihydro-A-methylhasubanan (40), 3,9a-dihydroxy-N-methylhasubanan (69), 3,9a-dihydroxy-A-cyclopro-pylmethylhasubanan (70), and 3-hydroxy-A-cyclopropylmethylhasubanan... 

Analgesic and Narcotic Antagonist Activity of Some Hasubanan Alkaloids in Mice"... 

Displacement Potency of Hasubanan Alkaloids on the Specific Binding to Rat Brain Homogenates of [3H]Etorphine ... 

However, the affinity of 43 was higher than that of the allylic derivative 72 and near to that of codeine, though 5-fold less (74). Recently, some naturally occurring hasubanan alkaloids have been submitted to screening for antitumor activity, but the results, as far as we know, remain obscure. 

Another application of this strategy is the construction of cyclic systems bearing 1,4-dissonant relationships. For example, the synthesis of the hasubanan alkaloid ring system 35. reported in 1972 by Evans [24], involves the Diels-Alder cycloaddition of a dienyl sulphoxide 32 with an endocyclic enamine 33, followed by a [2,3]-sigmatropic rearrangement of the resulting cycloadduct 34 (Scheme 5.21). 

A route to hasubanan alkaloids has been described involved reaction of 1-butadienyl phenyl sulfoxide with the tetrahydrobenzindole D. Treatment of the resulting adduct with sodium sulfide in refluxing methanol gave F. Suggest a structure for E, and rationalize the formation of F from E. 

Trauner, D., Porth, S., Opatz, T., Bats, J.W., Giester, G., Mulzer, J. New ventures in the construction of complex heterocycles. Synthesis of morphine and hasubanan alkaloids, Synthesis 1998, 653-664. 

Two new hasubanan alkaloids, nordelavaine (56, C19H21NO5) and stephanubine (57, C20H25NO5), have been isolated from the tuberous roots of Stephania suberosa along with the known hasubanan delavaine (39). 

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