Strychnos akuammicine

Rosenmund group never applied this reaction to the Strychnos alkaloids (e.g., akuammicine, 58) is somewhat surprising. 

Alkaloids like preakuammicine (Figure 6.79) and akuammicine (Figure 6.75) contain the C10 and C9 Corynanthe type terpenoid units respectively. They are, however, representatives of a subgroup of Corynanthe alkaloids termed the Strychnos type because of their structural similarity to many of the alkaloids found in Strychnos... 

Strychnine-Akuammicine-Ellipticine Group. 11-Methoxyicajine (110)77 and 15-hydroxystrychnine,78 a new alkaloid, have been isolated from Strychnos nux-vomica seeds, and 11-methoxydiaboline from S. rubiginosa.58 10-Hydroxy-akuammicine (sewarine) occurs in the leaves of Rauwolfia volkensii,60 and 11-methoxyakuammicine in Alstonia odontophora.59... 

Strychnine-Akuammicine-Ellipticine Group. A new alkaloid encountered in the culture of cell line 943 of Catharanthus roseus has been formulated, on the basis of its n.m.r. and mass spectra, as the /S-xyloside (147) of 9- (or 12-)hydroxy-akuammicine.42a Akuammicine and 10-methoxyakuammicine are reported to be present in the leaves of Rauwolfia oreogiton.43a Diaboline has been found in the root bark of Strychnos jobertiana Baill., and 11-methoxydiaboline in the root bark of S. 

Researches carried out to the early part of 1966 have been comprehensively reviewed and the present account will set out from that point. In brief, the situation reached at that time was as follows. Despite their bewildering variety, three main groups of alkaloids had been recognised (a) the Corynanthe-Strychnos type, e.g. ajmalicine (1) and akuammicine (2) which possess the non-tryptamine unit (3), (b) the Aspidosperma type, e.g. vindoline (4), in which the non-tryptamine unit appears as (5), and (c) the Iboga type, e.g. catharanthine (6), having still a different arrangement of the non-tryptamine unit (7). 

Strychnine-Akuammicine-Condylocarpine-Uleine Group. Several variations of the strychnosplendine (62) theme isolated from Strychnos splendens have been examined in detail. A careful investigation has elucidated the complete pathway by which strychnine or its metho-salt can be degraded to the Wieland-Gumlich aldehyde or its metho-salt Sodium-ammonia cleavage of dihydro-strychnidine A methosulphate gives (63). 

Geissoschizoline [= pereirine (106)] is an indoline derivative with a Strychnos carbon keleton. The complete structure was elucidated by partial synthesis from (—)-akuammicine (117) the latter on reduction with zinc and acid forms 2/ ,16jS-dihydroakuammicine which on lithium aluminium hydride reduction followed by catalytic hydrogenation gives geissoschizoline (106). The base can also be obtained by degradation of the strychnine derivative (1IS). " ... 

For the stereocontrolled synthesis of hexahydro-l/f-pyrrolop -rflcarbazoles, potential intermediates for the synthesis of the Strychnos alkaloid akuammicine, see ref 1142. 

Since the last review on Picralima alkaloids was written (for Volume X) activity in this field has considerably abated and in consequence there is comparatively little new work to be reported. The main features of indole alkaloid biosynthesis have now been elucidated and the reader is referred to Battersby (1) for an authoritative summary of this fascinating topic. Preakuammicine (1) appears to be involved in the direct pathway to the Strychnos, Aspidosperma, and Iboga alkaloids, and although it has not been isolated from Picralima it is appropriate to include it here, and to note that its presence in very young seedlings of Vinca rosea has been established (2). Preakuammicine is almost certainly the precursor of akuammicine (2), a transformation which can also be achieved by treatment with base (2). 

The third total synthesis of strychnine (1), so far the only enantioselective route to the natural product, was accomplished by Overman et al. [10] The key to their approach to 1 is the sequential cationic aza-Cope rearran-gement/Mannich cyclization, which is frequently employed with success in alkaloid synthesis. With the synthesis of akuammicine rac-19 the authors proved that this strategy offers an efficient route to the strychnos alkaloids. [8g]... 

Strychnine-Akuammicine-Condylocarpine-Ellipticine Group. Full details have been given of structural work on hunteracine chloride and of Le Goffic s synthesis " of ellipticine reviewed" in Volume 4. It has been shown that the so-called strychnicine, isolated from leaves of Strychnos ignatii and S. nux-vomica many years ago, is probably vomicine. 11-Methoxydiaboline occurs... 

A more significant result is the twofold cyclization that completes the pentacyclic skeleton of certain Strychnos alkaloids. The product is converted to akuammicine in two more steps. 

Bonjoch J, Sole D, Garcia-Rubio S, Bosch J (1997) A General Synthetic Entry to Strychnos Alkaloids of the Curan T pe via a Common 3a-(2-Nitrophffliyl)hexahydroindol-4-one Intermediate. Total Syntheses of ( )- and (-)-Tubifolidine, ( )-Akuammicine, ( )-19,20-Dihydroakuammicine, ( )-Norfluorocurarine, ( )-Echitamidine, and ( )-20-Epilochneridine. J Am Chem Soc 119 7230... 

Preakuammicine (19) serves as an efficient precursor of akuammicine (20) (a class 1 Strychnos alkaloid) and vindoline (9) (an Aspidosperma alkaloid). When labeled stemmadenine (21) (a Strychnos alkaloid) (class 1) was fed to Catharanthus roseus plants, labeled tabersonine (24) (class 1), vindoline (9) (class 3), and catharanthine (10) (class 5) were produced. Thus, preakuammacine (19) and stemmadenine (21) serve as key intermediates of both class 3 and 5 alkaloids. It has been proposed that incorporation of stemmadenine (21) into vindoline (9) and catharanthine (10) proceeds via dehydrosecodine (25). A Diels-Alder reaction could lead to the formation of tabersonine (24) and catharanthine (10), respectively (Fig. 34.5). 

Simple rearrangement of the Corynanthe skeleton [as [6.243)] affords the Strychnos type, exemplified by akuammicine [6.242), and strychnine [6.263). Like [6.242), strychnine has been found to have the expected origins in tryptophan and in mevalonate via geraniol the extra C2 unit (C-22 and C-23) arises from acetate. Late intermediates have been identified and the pathway deduced is shown in Scheme 6.47 [182]. 

The Strychnos alkaloids possess diverse chemical structures that have attracted considerable attention in organic synthesis during the last decades. Recent studies on the synthesis of akuammicine, strychnine and leuconicine A and by Andrade et al. proved that the intramolecular Heck reaction is extremely valuable for the construction of complex polycyclic molecules. Based on Rawal s method for the construction of the D ring of Strychnos alkaloids, vinyl iodides 37, 39, and 42 undergo a regioselective and stereoselective palladium-catalyzed cychzation in the presence of Pd(OAc)2, PPha in Et3N to furnish ( )-akuammi-cine 38, and the advanced intermediates 40 and 43 in excellent chemical yields (Scheme 13.11). 

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