Indolizi dines

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... 

In efforts designed to replace the imidazopyridine ring system, indolizi-dines such as (32) [101] (human H3 if = 13 nM), and related heterocycles [102-104] were identified as potent H3 antagonists. Indolizidine (32) suffered from rapid metabolism in human liver microsomes, however, substitution on the indolizidine ring suppresses this liability. 

Several reductive cyclizations have been used to obtain the indolizi-dine system4 of which the route shown in Eq. (24), used by Carelli and his associates, is an example.235... 

Formic acid has been used to cyclize ethoxylactams to indolizi-dines.245-240 Thus, 186 was converted stereospecifically into 187 [Eq. (25)].24s... 

In a study aimed at the scope and limitations of SET-photoinduced synthesis of indilizidine and quinolizidine ring forming, a-amino radical cyclization reactions are explored.349 It was shown that 2-silyl-pyrrolidyl and piperidyl enones react nicely under DCA-sensitized irradiation (A > 320 nm) in degassed acetonitrile to produce indolizi-dine and quinolizidine compounds. This technique appears as efficient as the preceding one (DCN in protic medium).344... 

Rather similar degradation processes are reported for the indolizi-dine alkaloid securinine.66... 

Fig. 10. Structures of 3,5-disubstituted pyrrolizidines from dendrobatid and ranid frogs andbufonid toads (31,73,81, and J. W. Daly, H. M. Garraffo, andT. F. Spande, unpublished). Absolute configurations are unknown. It is assumed, based on analogy to other amphibian alkaloids, that n-alkyl side chains are present. The configurational nomenclature for these pyrrolizidines follows the system devised by Sonnet el at. (122) for 3,5-disubstituted indolizi-dines where the H-S and H-8 configurations are related to that at H-3 and are either cis (Z) or trans (E).

Michael JP, Gravestock D (1997) Enaminones as intermediates in the synthesis of indolizi-dine alkaloids. Pure Appl Chem 69 583-588... 

Nitrone 81 underwent a dipolar cycloaddition reaction with bicyclopropylidene 82 at 60 °C over a 30-day period to give isoxazolidine 83 in 93% yield (Scheme 14) (96JOC1665). Further heating of 83 in toluene at reflux for 5 days produced pyridone 84 in 63% yield. When a toluene solution of 81 and 82 was heated at reflux for several days, pyridone 84 was isolated in 61% yield. Nitrone 85 produced indolizi-dine 86 when heated with 82 in benzene at reflux temperatures for 7 days. 

Pd(II)-mediated cascade cyclizations have also been employed for the construction of other types of heterocyclic systems. For example, Backvall reported that the oxidative cyclization of dienyl amides occurred to give pyrrolizidines and indolizi-dines. Thus, treatment of 629a,b with Pd(OAc)2 and CuCl2/02 provided 630a,b in 90 and 85% yield, respectively (Scheme 104) (92JA8696). 

Intramolecular aSH reaction could be effected by treating the enamide with 4 equivalents of TFA, which resulted in the formation of the indoli-zidine 39 in a yield of 89%. The diastereomeric ratio was 90 10 in favor of the cis stereoisomer. When the enamide 36 was subjected to the conditions of hydroformylation and then the TFA was added, the indolizi-dine 39 was also obtained in 82% yield, higher than the two-step procedure (69%) and an identical diastereomeric ratio was observed. The hydroformylation reaction of the indolizidine 39 gave the aldehyde 40 in 78% yield. 

Pumdiotoxins (PTX). Alkaloids isolated from the arrow poison frog Dendrobates pumilio with indolizi-dine (P. A and B) or decahydroquinoline skeletons (P. C). The P. were later also detected in other frogs and toads. ... 

C8H,oN20, Mr 150.18, mp. 122-123°C. An indolizi-dine alkaloid from a Thermoactinomyces species (Ba-cillaceae) found in a hot spring of Lake Tanganyika. Lit Angew. Chem., Int. Ed. Engl. 35, 545IT. (19%). 

The chiral amino ester 1999, previously used in a synthesis of (—)-indolizi-dine 209B (1876) by Bardou et al. in 1998, was the starting material in the synthesis of both (—)-1876 and (—)-indolizidine 207A (1554) by Back and Nakajima (Scheme 252). The chloroalkyl amine (+)-2000, made in three steps from 1999, reacted readily with the alkynylsulfones 2001 or 2002 to give the unsaturated indolizidines (—)-2003 and (—)-2004, respectively. In this example, the six-membered ring is formed by C-6/C-7 bond formation. Diastereoselective reduction of the conjugated double bond in the... 

The group of Sas developed a novel synthetic route to polyhydrojqrlated indolizi-dines (Scheme 8). Protected a-D-mannofuranoside 41 was transformed into derivative 43 by reaction with hydroiq lamine 42 (nitrone formation) followed by intramolecular 1,3-dipolar cycloaddition. This compound was transformed into ammonium salt 44, which was then cleaved under the basic conditions, giving the desired indolizidine scaffold 45. Alternatively, compound 43 was transformed into the mesyl ester 46, which cyclized upon treatment with K2CO3, providing the bicyclic compound 47. 

Wrohleski A, Sahasrabudhe K, Aube J. Asymmetric total synthesis of dendrobatid alkaloids preparation of indolizi-dine 25 IF and its 3-desmethyl analogue using an intramolecular Schmidt reaction strategy. J. Am. Chem. Soc. 2004 126(17) 5475-5481. 

D (301 and 300, Scheme 24.73). The exposure of 298 in formic acid at 100°C led to the clean formation of indolizi-dine 299 in excellent yield. Further five-step conversion from 299 led to 300, which was further converted into 301. 

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