Pyridine monoterpene alkaloid

The intent of this chapter is to provide an update of pyridine and piperidine alkaloid literature since this topic was last covered in Volume 3 of this series [1], The approximate time period covered by this review is 1984-1994. Due to the wealth of information available, this review had to be somewhat selective. For example, with the exception of a few selected pyridine monoterpenes, alkaloids containing a pyridine or piperidine ring fused to another ring system were excluded. The focus of this review is placed on describing new compounds isolated, biosynthesis, and biological properties. Synthesis has not been emphasized in most cases reference is made to only the most recent syntheses. 

Roby, M. R. and Stermitz, F. R. (1984) Penstemonoside and other iridoids from Castilleja rhexifolia. Conversion of penstemonoside to the pyridine monoterpene alkaloid rhexifoline J Nat Prod 47, 854-857. 

Roby, M. R. and F. R. Stermitz, Pyrrolizidine and pyridine monoterpene alkaloids from two Castilleja plant hosts of the plume moth, Platyptilia pica, J. Nat. Prod., 47, 846-853 (1984). 

Gentiananine (93) represents the first of a new series of monoterpene alkaloids in which the pyridine ring is fully substituted. Biogenetically, the alkaloid may arise from a secologanin precursor through complete opening,... 

Heterocyclic ring formation can then lead to a piperidine or a pyridine-type ring system, giving rise to the two principal groups of monoterpene alkaloids ( fig. 9 ). 

There has been substantial progress in the synthesis of the monoterpene pyridine alkaloids in the past 23 years. Particularly, this progress has oc-... 

An interesting new approach to monoterpene pyridine alkaloids has been described recently by Vidari and co-workers (206), based on the ability of a Schmidt reaction to desymmetrize bicyclo[3.3.0]octane-3,7-dione (249). This was achieved through reaction with sodium azide and boron trifluoride in CH2CI2 H20 (1 1) at 25°C for 3 h, which gave the lactam 250 in 25% yield. This could be increased to 50% yield by reacting 249 with sodium azide and cone. HC1. Ketalization followed by N-methylation with a phase transfer catalyst gave the lactam 251. Monomethylation of 251 afforded... 

When antirrhinoside (318) was reacted under the standard conditions, the dihydroxy acetate monoterpene pyridine alkaloid derivative 319 was produced cleanly in about 10% yield (224). The structure was deduced spectroscopically. An acetate group was apparent (8h 2.1 Sc 21.9,172.6) and doublets (J = 5.6 Hz) at 4.31 and 5.11 ppm. The latter showed an NOE with H-4 and was therefore assigned to H-6. X-ray crystallography affirmed the acetate group to be located at C-8 and defined the stereochemistry of C-6 and C-7 to be as shown in 319. 

Physical and Spectroscopic Data of Monoterpene Pyridine Alkaloids and Derivatives 1... 

As noted in the discussion of the in vitro conversion of the iridoids to the monoterpene pyridine alkaloids (see Section III.G), frequently the iridoid corresponding to the alkaloid is a co-metabolite in the isolation process or a direct progenitor, based on the isolation procedure when ammonia is used. Similarly, one can envisage, with the studies on the planned generation of alkaloids from iridoids (see Section III.H), that alkaloids can be produced semisynthetically that may subsequently be found in nature. 

The whole plant of Incarvillea sinensis is used in traditional Chinese medicine as an antirheumatic and analgesic (88). Examination of the alkaloid content led to a number of new monoterpene pyridine alkaloids discussed earlier (see Section II.A.20-22). Biological evaluation of the isolates indicated that incarvillateine (34) at 10 mg/kg i.p. inhibited both the first and second stages of formalin-induced pain and reduced spontaneous motor activity. At lower doses (1-5 mg/kg), the analgesic activity was maintained without sedative activity (88). 

Alkaloids that possess an aromatic pyridine ring often are called pyridine alkaloids (Leete, 1980 Pinder, 1993 Strunz and Findlay, 1985) approximately 250 alkaloids of this type are known (Verpoorte et al., 1991). Although many are derived from nicotinic acid (Fig. 28.18), others arise from aro-matization of piperidine alkaloids and other pathways (Waller and Nowacki, 1978). This chapter includes several of the most important compounds of this type, although others (such as a number of monoterpene-derived alkaloids, Nu-phar alkaloids, and sesquiterpene alkaloids of the Celastra-ceae) are discussed in Chapter 36. 

This is an example of a bicyclic ring system with the fusion of benzene and pyridine rings. Biosynthetically they are related to indole alkaloids since both groups are derived from the same two precursors, tryptophan and loganin—a monoterpene iridoid (Samuelsson 1992). 

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