Indolizidines

The occurrence of the indolizidines, with the exception of ipomine, turned out to be not limited to the seeds. Ipalbidine and ipohardine were detected in the roots as well as in the epigeal vegetative parts of I. alba and I. turbinata, ipalbine only in the roots of the latter species. However, the concentrations were considerably lower in these vegetative parts compared with the seeds. Furthermore, ipalbine and ipohardine, hitherto only known as constituents of the two other species, could also be detected in the seeds of I. turbinata (Tofern et al. 1996 Tofern 1999). 

Interestingly, traces of ipalbidine could be identified by GC/MS analysis in the aerial parts of Convolvulus caput-medusae Lowe, C. scoparius L. f (Schimming 2003), Ipomoea batatas (L.) Lam., I. eremnobroclia D.F.Austin, and Odenellia hirtiflora (Mart. Gal.) K.Rob. (Tofern 1999). This indicates that the principal capability to synthesize this type of alkaloids might be widespread in the family. 

29 Structure of nedne bases occurring in pyrrolizidme alkaloids from the Convolvulaceae 

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An intramolecular version offers useful synthetic methods for heterocycles. The total syntheses of a- and 7-lycoranes (373 and 374) have been carried out by applying the intramolecular aminochlorination of the carbamate of 5-(2-aminoethyl)-l,3-cyclohexadiene (372) as a key reaction[312,313]. Interestingly, the 4,6- and 5,7-diene amides 375 and 377 undergo the intramolecular amina-tion twice via x-allylpalladium to form alkaloid skeletons ofpyrrolizidine (376) and indolizidine (378), showing that amide group is reactive[314]. 

Cinnolin-4(lH)-one, 8-hydroxy-iodination, 3, 21 Cinnolin-4-ones synthesis, 3, 56 Circular dichroism indolizidines, 4, 450 pyridines and benzo derivatives, 2, 126... 

Diphosphirane, 1,2-di-t-butyl-synthesis, 7, 196 Dipole moments indolizidines, 4, 450... 

Loffler-Freitag reaction, 4, 471 Indolizidine, 3-butyl-5-methyl-occurrence, 4, 477... 

Indolizidine, 5,7-dimethyl-conformations, 4, 451 Indolizidine, 3,5-dioxo-IR spectra, 4, 450 reactivity, 4, 462... 

Indolizidine, 6-(3-furyl)-8-methyI-occurrence, 4, 477 Indolizidine, hydroxy-basicity, 4, 461... 

Indolizidine, 1 -hydroxy-2-methyl-synthesis, 4, 471 Indolizidine, 1-hydroxy-3-oxo-benzoylation, 4, 461 Indolizidine, 3-methyl-synthesis... 

Dieckmann reaction, 4, 471 Indolizidine alkaloids mass spectra, 4, 444 Indolizidine immonium salts reactions, 4, 462 Indolizi dines basicity, 4, 461 circular dichroism, 4, 450 dipole moments, 4, 450 IR spectra, 4, 449 reactivity, 4, 461 reviews, 4, 444 stereochemistry, 4, 444 synthesis, 4, 471-476 Indolizine, 1-acetoxy-synthesis, 4, 466 Indolizine, 8-acetoxy-hydrolysis, 4, 452 synthesis, 4, 466 Indolizine, I-acetyl-2-methyI-iodination, 4, 457 Indolizine, 3-acyloxy-cyclazine synthesis from, 4, 460 Indolizine, alkyl-UV spectra, 4, 449 Indolizine, amino-instability, 4, 455 synthesis, 4, 121 tautomerism, 4, 200, 452 Indolizine, 1-amino-tautomerism, 4, 38 Indolizine, 3-amino-synthesis, 4, 461, 470... 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

The intramolecular cycloaddition reaction of enamides has been exploited in alkaloid synthesis (81JOC3763). One successful application is provided by the total synthesis of the fused indolizidine 5 from 4 as a 1 1 mixture of epimers in 43% total yield 5 is a key intermediate in aspidosperma alkaloid synthesis (79JA3294). 

Tetrahydropyridines 103 undergo a Michael reaction to afford [ran.s-(2,3)-cis-(2,6)-trisubstituted piperidines 104 (97T9553). The reaction is stereoselective (a single stereoisomer was obtained) and provides a convenient route to the 5,8-disubstituted indolizidine 105 and 1,4-disubstituted quinolizidine system 106 (found in Dendrobates alkaloids) by introduction of various alkyl, alkenyl, or... 

The intramolecular cyclization of l-(4-bromobutyl)-3-methoxycarbonyl-l,4,5, 6-tetrahydropyridine (140) and l-(3-bromopropyl)-3-methoxycarbonyl-l,4,5,6-tetrahydropyridine (143) (89T5269) resulted in the synthesis of quinolizidine ring system 141 and indolizidine ring system 144 in 43% and 72% yields along with the reduced tetrahydropyridines 142 and 145 in 21% and 8% yields, respectively. All the cyclized products appeared to be (ran.s-fused indolizidines or quinolizidines. The (ran.s -fused simple indolizidines are known to be some 2.4 kcal mol more stable than the d.s-fused isomers (68TL6191). In the and-isomer the methoxycarbonyl substituent occupies an equatorial position. 

Pyrrolizidine and indolizidine syntheses involving 1,3-dipolar cycloadditions 99S905. 

The aza-[2,3]-Wittig rearrangement of a vinylaziridine-derived quaternary azir-idinium ylide (i.e., [2,3]-Stevens rearrangement) has recently been reported (Scheme 2.53) [86], The aziridinium ylide 219, generated by the intramolecular reaction of a copper carbenoid tethered to a vinylaziridine, underwent a [2,3]-Ste-vens rearrangement to furnish the bicydic amine 220 with the indolizidine skeleton. 

A novel approach to azabicyclic ring systems, based on an epoxide-initiated electrophilic cyclization of an alkyl azide, has been developed by Baskaran. A new stereo- and enantioselective synthesis of the 5-hydroxymethyl azabicyclic framework 91a, present in (+)- and (-)-indolizidines 167B and 209D, for example, was... 

Die selektivc Reduktion von Cyan-dicarbonsaure-imiden untcr Erhalt der Cyan-Grup-pen ist mit Lithiumalanat nicht durchzufiihren8. Die Methode ist zur Herstellung von Ringsystemen mit Stickstoff als Briickenkopf-Atom (z. B. Pyrrolizidin, Indolizidin) besonders geeignet13. 

A review article is an intensive survey of a rather narrow field for example, the titles of some recent reviews are Desulfonation Reactions Recent Developments , Pyrrolizidine and Indolizidine Syntheses Involving 1,3-Dipolar Cycloaddtion , and From Corrin Chemistry to Asymmetry Catalysis—A Personal Account. A good review article is of enormous value, because it is a thorough survey of all the work done in the field under discussion. Review articles are printed in review journals and in certain books. The most important review journals in organic chemistry (though most are not exclusively devoted to organic chemistry) are shown in Table A.3. Some of the journals listed in Table A.l, for example, the Bull Soc. Chim. Fr. and J. Organomet. Chem. also publish occasional review articles. 

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