Alkaloids pyrroline

Pyrrolidine alkaloids have a pyrrolidine (C4N skeleton) nucleus. The structural a of these alkaloids is L-ornithine (in plants) and L-arginine (in animals). The pyrro-line skeleton is synthesized after /3 (putrescine) and

Schiff base reaction forms which is A-methyl-A -pyrrolinium cation. Subsequently, A (hygrine) is formed. Typical pyrroline alkaloids are (-)- and (-1-)- hygrines (Figure 56). 

Pyridone alkaloids 100, 101 Pyridostigmine 119 Pyrrole alkaloids 168 Pyrrolidine alkaloids 7, 63, 103, 104 Pyrroline alkaloids 103 Pyrrolines 103... 

The bioactive secondary metabolites reported from Broussonetia kazinoki can be classified into major two groups, alkaloids and flavonoids (Table 1), Fig. (1). The Kusano group at Osaka University of Pharmaceutical Sciences in Japan reported over 20 pyrrolidine alkaloids, broussonetines A-H, K-M, O-T, V-X, and Mi, and broussonetinines A and B, four pyrrolidinyl piperidine alkaloids, broussonetines I, J, Ji, and J2, two pyrroline alkaloids, broussonetines U and U, and one pyrrolizidine alkaloid, broussonetine N, from hot water extracts of B. kazinoki [16-24]. As shown in Table 1, some of these alkaloids exhibited strong... 

The opening of activated cyclopropanes with nitrogen nucleophiles has been widely applied to the synthesis of pynolizidine and pyrroline alkaloids by Danishefsky this subject has been reviewed. A number of pyrroline annulations have been based on this principle, illustrated in equation (35a). > Similar opening can be accomplished with halides, cuprates, and sulfur or selenium nucleophiles. ... 

Finally, it is worth mentioning that the pyrroline alkaloid nectrisine (Figure 2), which inhibits a-glucosidases in addition to a-mannosidases, has been reported to restore the immune response of immunosuppressed mice. ... 

True alkaloids L-ornithine Pyrroline alkaloids Pyrrolidine Cuscohygrine Hygrine... 

Broussonetines are a family of about 20 pyrroline alkaloids obtained from Broussone-tia kazinoki Sieb. (Moraceae) during 1997 to 2001, possessing an 18-carbon chain skeleton [38-46]. In this section, we deal only with broussonetine J because biosynthetic studies have been conducted on this derivative. Broussonetine J was isolated with broussonetine I, and to them were assigned the structures 13 and 14, respectively (Figure 5.6) [41]. 

Ornithine-Derived Alkaloids. Ornithine (23) undergoes biological decarboxylation reductively to generate either putrescine [110-60-1] (36), or its biological equivalent, and subsequent oxidation and cyclization gives rise to the pyrroline [6724-81-2], (37), C H N. 

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

A -Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite (71), persulfate (102), and periodate (103). A -Pyrroline and A -piperideine are products of enzymic oxidation via deamination of putrescine and cadaverine or ornithine and lysine, respectively (104,105). This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, especially of alkaloids. 

The piperideine derivatives have not been studied as extensively as the analogous pyrrolines (151,152). The imino structure has been established, for example, for the alkaloid y-coniceine (146) (46). The great influence of conjugation on the structure is seen with l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline (47), possessing an enamine structure, whereas the analogous 1-methyl derivative (48) possesses an imine structure according to infrared spectra (152,153). 

From a vast number of alkaloids containing the /I -pyrroline or piperideine ring in the molecule, alkaloids myosmine (197) and lobinaline (i/5) (198) of Lobelia cardinalis L. may be mentioned. 

Hudlicky and coworkers also reported a related 2-pyrroline formation from viny-laziridines [81], which are extremely useful for the synthesis of pyrrolizidine alkaloids such as the protected (+)-trihydroxyheliotridane 210 (Scheme 2.51). Since the pyrolysis of either diastereomer of 208 furnished the cyclized product 209 as a... 

Besides piperidine alkaloids, a total of 19 pyrrolidines have been found in the secretions of thief ants and fire ants of the genera Solenopsis and Monomorium. Among these, compounds 80-84 are simple pyrrolidines with two saturated linear all-carbon side chains only in Solenopsis latinode is there a secondary amine (82) and its methylated analog (85). One or two terminal unsaturations are present in compounds 86-91, which all possess a (hex-l-en)-6-yl chain and a 5-, 7-, or 9-carbon saturated chain. Compounds 93, 94, 96, 97, and 98 are the A-l-pyrrolines corresponding to pyrrolidines 80, 82, 90 (93 and 96 corresponding to 80, 94 to 82, and 97 and 98 to 90). 

The syntheses of flavanoid alkaloids also rest on A-l-pyrroline chemistry and on Friedel-Crafts-type reactions. In Govindachari s pioneering synthesis of ficine (167), pyrrolidine 126 is formed by condensation of trimethoxybenzene and y-aminobutyric acid in the presence of PPA (Scheme 19). Although the mechanism of this reaction has not been precisely determined, it may involve a A-l-pyrrolinium cation. These conditions were later used by Koch et al. in their synthesis of vochysine (Scheme 20) (108). 

Curiously, the synthesis of shihunine via a phenylcyclopropylimine (187) is the sole example of a simple pyrrolidine alkaloid obtained according to this general pyrroline synthesis (188) (Scheme 40). 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Phenyl-1-pyrroline is useful for various purposes.10 11 In particular, its reduction product, 2-phenylpyrrolidine, is important in the synthesis of pyrroloisoquinoline antidepressants,20 12 and can be a starting point in alkaloid synthesis.13 The overall reaction sequence described here has been used to prepare nicotine derivatives such as myosmine.2a b... 

The alkaloid tylophorine was synthesized from ornithine. Ornithine was first converted into 1-pyrroline which gave the alkaloid septicine 68 after several transformation steps. This alkaloid was then oxidized into tylophorine [82JCS(P1)2477]. 

Figure 33. Synthesis of alkaloids from ornithine. Aikaioids are derived via putrescine or glutamic semialdehyde. At least two enzymes, ODL (Ornithine decarboxylase) or PDL (Pyrroline...

Tropane alkaloids have a tropane (C4N skeleton -f) nucleus. Structurally, these alkaloids synthesize as postcursors of pyrrolines (Figure 57). a, /3,

tropane alkaloids (e.g., atropine, hyoscyamine, cocaine, tropinone, tropine, littorine and cuscohy-grine) have a strong biological activity, especially as neurotransmitters. 

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

An impressive number of alkaloids has been generated from the synthon (202), which is accessible by an acid catalyzed rearrangement of the appropriately substituted cyclopropyl-imine. The endocyclic enamine (202) should react with electrophiles on the /8-carbon in a process which simultaneously renders the a-carbon electrophilic and therefore susceptible to capture by nucleophilic reagents. The application of this methodology to the synthesis of ipalbidine (191a) and septicine (204) is shown in Scheme 30. Here, the unusual 3-phenylthio-2-pyrroline intermediate (203) serves as a relatively stable equivalent synthon of the unsubstituted 2-pyrroline analogue which is notoriously unstable (77ACR193). 

A stereoselective entry into the 3,5-dialkylindoIizine alkaloid area proceeding via N(l)—C(2) vicinal annelation of a 1,4-dibromoalkane on to a pyrroline system has been described (80JOC193). 

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