Alkaloids Dieckmann reaction

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... 

Most of the oxoindolizidines have been prepared by Dieckmann reaction or related condensations. Thus (188) was used to prepare (189), which is a precursor for the synthesis of 2-methyl-1-hydroxyindolizidine (190) (70AP812). Ipalbidine (191a), which is one of the Ipomea group of alkaloids, was prepared as outlined in Scheme 26 (71HCA513). 

The amino acid derived carboxy group can be utilized as a functionality for further synthetic manipulations, e.g. for cyclization reactions to 1,3-bridged P-carbolines, using the Dieckmann reaction, a promising stereocontrolled approach to macroline-related alkaloids (Scheme 14). > ... 

During synthetic studies on the benzophenanthridine alkaloids, the nitrile ester 1 was treated with sodium hydride in THF in the expectation that a Thorpe-Dieckmann type of reaction would... 

The total synthesis of (+ )-dehydroheliotridine (4), a toxic metabolite of the pyrrolizidine alkaloids (e.g. lasiocarpine and heliotrine), has also been described.2 The pyrrole ring was obtained by reaction of l,6-dihydroxy-2,5-dicyanohexa-l,3,5-triene-l,6-dicarboxylic ester (5) with j3-alanine, which afforded the N-substituted pyrrole ester (6), together with the appropriate amide of oxalic acid. Careful hydrolysis of (6) with dilute alkali afforded the related tricarboxylic acid, which was converted, by Dieckmann cyclization, hydrolysis and decarboxylation, into the keto-acid (7). Esterification of (7) with diazomethane, followed by reduction with lithium aluminium hydride, finally afforded ( )-dehydroheliotridine (4), identical, except in optical rotation, with dehydroheliotridine obtained earlier by Culvenor et al.3... 

Intramolecular base-promoted cyclization of suitable diesters (Scheme 52) is one of the earliest routes to benzo[a]quinolizidines, which was exploited in the synthesis of racemic emetine developed by Oppenshaw <53JCS2463>. Reaction of tetrahydroisoquinoline (255) with ethyl a-formylbutyrate followed by hydrogenation afforded (256), which was cyclized by base to yield (257), the benzo[a]-quinolizidine portion of the alkaloid. On this occasion only one of the two possible Dieckmann condensation products was observed, although this has not always been the case with related cyclizations <73BSF3476>. 

Reagent-based and substrate-based approaches can also be combined in a single two-directional synthesis in which different symmetrical substrates can be used under different reaction conditions to achieve predictable scaffold diversity [23]. In an example by Spring et al, two domino reactions were used to synthesize polycyclic alkaloids from a common substrate 147. A Boc-removal/bicyclization process using AlClj as Lewis acid from 147 was used to produce 5-5, 5-6, and 6-6 bicyclic compounds (148-153), and a domino Michael addition/Dieckmann process/Michael addition reaction yielded 6-6-6, 6-6-5 tricyclic compounds (154-156). The 6-5-5 tricyclic scaffold 156 could not be synthesized by means of the same domino... 

A final illustration of how Dieckmann cyclizations have been utilized in yohimbine alkaloid synthesis is found in the work of Winterfeldt and coworkers (59, 60). In these studies, this methodology was employed to construct the pentacyclic alkaloid skeleton found in thioketal 335 (Scheme 3.55). Reaction of j5-enaminoester 327, prepared by condensation of tryptamine and... 

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