Piperidine rings, alkaloids with

Chiral epoxide 56 was opened with suitable alkyne 57 (bearing alkyl chain present in the tail of the alkaloid) followed by TBS protection of alcohol that provides diamine 59. Diamine 59 undergoes Ag-catalyzed reductive hydroamination to produce piperidine ring 60 with correct stereochemistry as present in the alkaloid. Finally, the TBS group is deprotected to produce (-p)-pseudodistomine D 61 in quantitative yield (Scheme 39.15). 

In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

Nicotiana species and certain lupine species also contain potent toxic and teratogenic piperidine alkaloids (Figure 2.4). All teratogenic piperidine alkaloids have specific structural characteristics that are responsible for induction of birth defects. Their molecular structures include a piperidine ring, with a side chain of at least three carbons or larger attached adjacent to... 

In the course of our synthetic efforts, we discovered a new, unnatural conformational isomer of the VBL piperidine ring (see Chapter 2, this volume, for details). This compound is inactive with the microtubule system in vitro and is poorly cytotoxic to cultured tumor cells (Fig. 5b). Therefore, the functional determinism of the C-20 position of VBL-like molecules mediates reactions, as yet unknown, that are dependent on the binary alkaloid structure and on the natural stereochemical configuration at C-16 and C-14 as well as on the conformation of the cleavamine moiety. 

Pyridine alkaloids are compounds with a pyridine nucleus and a pyrrohdine or piperidine unit. The pyrrohdine ring appears in nicotine and the piperidine ring in anahasine. Typical alkaloids from this group are nomicotine and anatahine. The a of pyridine alkaloids is nicotinic acid, the j8 is dihydronicohnic acid, the q> is 1,2-dihydropyridine (Figure 61). The A is nicotine and its P is nomicotine. ... 

C-NMR spectral data have been recorded for vochysine (7) (5) and the Buchenavia alkaloids (8-16) (6) (Table V). In both cases comparison of the spectra with those of the parent flavonoid enabled the identity of this part of the molecule to be established. The chemical shifts of the A ring carbon atoms in some of the Buchenavia alkaloids have also been used to determine the point of substitution of the piperidine ring as described above, e.g., for buchenavianine (8). 

The rare reports of quinolizidine formation by a nitrone cycloaddition strategy include the racemic total synthesis of lasubine II (58), one of a series of related alkaloid isolated from the leaves of Lagerstoemia subcostata Koehne (Scheme 1.14) (104). While these alkaloids were previously accessed by infennolecular nitrone cycloaddition reactions, this more recent report uses an intramolecular approach to form the desired piperidine ring. Thus, cycloaddition of nitrone 59 affords predominantly the desired bridged adduct 60 along with two related... 

Alkaloids with Condensed Pyrrolidine and Piperidine Rings... 

The biphenyl group in both lactonic and metacyclophane alkaloids poses an interesting question about chirality. Ferris et al. (39) reported that the biphenyl moiety in lactonic alkaloids was inherently dissymmetric. Its chirality was determined by comparison of the circular dichroism (CD) curves with those of di-hydrothebaines with known chiralities. The biphenyl group of metacyclophane alkaloids with a piperidine ring, however, should exist as an equilibrium between two rotamers with (R) chirality (126a) and (5) chirality (126b) in solution as... 

Juliprosopine from Prosopis juliflora A. DC. is a new type of indolizidine alkaloid, and on the basis of an extensive spectroscopic and chemical study it has been assigned the structure (2), in which relative configurations are shown for the substituents on the piperidine ring. Juliprosopine may be derived biosynthetically from combination of a dihydropyrrole unit with two Prosopis piperidine alkaloids that have C12 side-chains.2... 

The coca-alkaloids, like cocaine, atropine, etc., contain perhaps a combination of a piperidine ring with a pyrrolidine ring. 

The monocyclic 2,6-disubstituted piperidines have been considered as possible precursors for dendrobatid alkaloids containing piperidine rings, such as the histrionicotoxins, decahydroquinolines, and gephyrotoxins (see Ref. J). Similarly, the monocyclic 2,5-disubstituted pyrrolidines have been considered as possible precursors for dendrobatid alkaloids containing pyrrolidine rings, such as the pumiliotoxins, the indolizidines, and now the pyrrolizidines (see Ref. 5). It should be noted that 2,6-disubstituted piperidines and 2,5-disubstituted pyrrolidines occur only rarely in dendrobatid frogs, while in ants they appear as major venom constituents, along with pyrrolizidines and indolizidines. It has been proposed that the monocyclic piperidines and pyrrolidines may serve as biosynthetic precursors of the bicyclic alkaloids in ants 125,134). 

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