Five-membered ring alkaloids

The simplest alkaloid families to which chemical shift correlation methods 

Kato et al. [68] reported the isolation and characterization of a novel imidazole antifungal alkaloid, fungerin (33) from the fungus Fusarium sp. The authors employed a GHMBC experiment optimized for 60 ms (8.3 Hz) to establish 

Fractionation of an alkaloid extract of Psychotria colorata flowers led to the isolation of six alkaloids, one of which was unknown. The new pyrrolidinoindoline alkaloid was, in part, characterized through the use of long-range GHMBC data as 

Later in 1998, two new pyrrole alkaloids were isolated and characterized from the berries of Solanum sodameum collected in the Libyan desert [70]. The structures were, in part, confirmed through the acquisition of GHMBC spectra. Long-range 

The next isolation and characterization of an imidazole alkaloid in which data were employed during the characterization is found in the work of Dunbar etal. [71] who reported a novel imidazole alkaloid, naamine-A 36, from the calcareous sponge Leucetta chagosensis. The authors did not report the optimization used to acquire the data. 

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For the most part, five-membered ring alkaloids tend to make one think of pyrrole- and imidazole-derived alkaloids. There are, however, also alkaloids that fall into this class that are, for example, derived from 1,2,4-thiadiazoles, for example, 19, the characterization of which is discussed Section 7.1.8. 

More advanced example The trans fused compound (13) was needed for a synthesis of some gclsemium alkaloids. Immediate Dlels-Aldcr disconnection is impossible as it would require an anhydride with a double bond in a five-membered ring. This would be fumarlc anhydride (14) but it does not exist. 

Raddeanamine (360) is an unusual spirobenzylisoquinoline alkaloid having a tertiary methyl group in five-membered ring. Methylation of the corresponding ketone gave the methyl carbinol with the reverse stereochemistry, namely, the methyl carbinol 361 was obtained from the reaction of the ketone 294 with methyllithium (Scheme 64). Stereoselective synthesis of ( )-raddeanamine was accomplished by an intramolecular oxyfunctionalization via the 8-methyl-8,14-cycloberbine 364 (175). 

Heteropines with fused five-membered rings are structural blocks of valuable natural products and their synthetic analogs. Latonduines 424 A (R = H) and B (R = COOH) (Eigure 9), two new alkaloids with pyrrolo-pyridoazepinone heterocyclic skeletons, have been isolated from the Indonesian marine sponge... 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The central five-membered ring of Manzamine A (315), a member of a family of antileukimic and antibacterial marine polycyclic alkaloids, has been constructed using intramolecular azomethine ylide technology (88). Model studies on the construction of the central ABC rings, by condensation of the aldehyde 316 prepared by standard chemistry with sarcosine ethyl ester, furnished the desired ABC ring system as a single diastereoisomer in 45% yield (Scheme 3.105). 

In the first synthesis of the hypotensive alkaloid (-)-ephedradine A 3 (Tetrahedron 2004,60, 9615), Tohru Fukuyama of the University of Tokyo faced the challenging of constructing the central five-membered ring ether with control of relative and absolute configuration. While neither chiral Rh catalysts nor chiral auxiliaries alone gave satisfactory results, a combination of the two worked efficiently, yielding the two trans diastereomers of 2 in a 13 1 ratio. 

Most cyclizations to form five-membered rings involve the 5-exo mode of cyclization. An exception has been reported in the intramolecular sulfenoamination of 3-alkenylamines used in the synthesis of pyrrolidine alkaloids (equation 102).215 229 Other examples include the aminomercurations of Af-sub-stituted-l-amino-3-butenes162,23° and the methylsulfenilium ion-initiated cyclization of 0-(2-propenyl)-/V-tosylaniline 231... 

These alkaloids are a relatively small group within the isoquinoline family. Ochotensimine (101) was the first to be studied and it and ochotensine are the only compounds of the group that have an exocyclic methylene on the five-membered ring (2, 3, 62). The most common functional groups are carbonyl, hydroxyl, or acetoxy at one or both of C-8 and C-13. The spectra of a series of these alkaloids were reported in 1977 (63) and these data were used recently in the structural elucidation of a new alkaloid (64). The structures and spectral data on the alkaloids discussed in this section may be found in Fig. 19 and Table XVIII, respectively. They are ochotensimine (101), sibiricine (102), corydaine (103), ochrobirine (104), fumaritine (105), and fumaritine A-oxide (106). 

Chiral enamine derivatives have also been used as electron-rich alkenes. The oxazoline derivative 17 reacted with benzaldehyde to yield the two stereoiso-meric oxetanes 18a and 18b with a diastereomeric excess of 67% (Scheme 5) [12]. A significantly higher diastereoselectivity was observed in the case of the reaction of the pyrrolidine derivatives 19 where the enamine function is localized inside the five membered ring [13]. Then the oxetane 20a (R — n-Cgil g) was used in an asymmetric synthesis of the antifungal alkaloid (+ )-preussin. The approach of the 3n,7T excited ketone preferentially occurred syn with respect to... 

Cepahalotaxine alkaloids are based on cephalotaxine which has a pentacyclic system including a seven-membered ring and a five-membered ring sharing an N atom (MD-Phe C6N C4 N G5 ). Cephalotaxine alkaloids include the cytotoxic, anticancer protein synthesis inhibitors cephalotaxine, harringtonine and homoharringtonine. 

Gardmultine (C45H54N4O10) a bisindole alkaloid isolated from Gardneria multiflora Makino, comprises gardneramine and chitosenine linked by a spiro five-membered ring. The structure proposed from chemical and spectroscopic properties (50) was confirmed by the crystal-structure analysis (51). The structural formula and the stereodrawing, shown in Fig. 25, illustrate the spiro junction at atom C-16 between the two component alkaloids of gardmultine. 

Synthesis from Steroidal and Alkaloidal Intermediates Steroidal intermediates have been employed in the synthesis of certain alkaloids such as dihydroconessine (58)(ref.55), one of the 3-aminoconanine bases, from the bile acid compound 3-B-acetoxybisnorcholenic acid, a substance obtained from appropriately-protected coprostanol by oxidation and two Barbier-Wieland degradations. The method consisted in converting the carboxyl into a formylamino group, the acetoxy into a tosylate which was then substituted by a dimethylamino group, reduction of the formylamino to methylamino and formation of the five-membered ring E by... 

This alkaloid (LXVII) is isomeric with kurchiline and shows close similarity to it in spectral data except for those pertaining to the ketone group. The position of the carbonyl band in the IR-spectrum (1748 cm i) demonstrated the keto group to be a part of a five-membered ring. This fact, in conjunction with strong negative optical rotation shown by the base, led to location of the ketone group in position 16. Both kurchi-... 

Research by M. Majewski et al. showed that the enantioselective ring opening of tropinone allowed for a novel way to synthesize tropane alkaloids such as physoperuvine. The treatment of tropinone with a chiral lithium amide base resulted in an enantioslective deprotonation, which resulted in the facile opening of the five-membered ring to give a substituted cycloheptenone. This enone was subjected to the Wharton transposition by first epoxidation under basic conditions followed by addition of anhydrous hydrazine in MeOH in the presence of catalytic amounts of glacial acetic acid. 

Other five-membered ring-containing alkaloids and natural products, including fused ring systems... 

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