Polyhydroxylated pyrrolizidines. Part 2: The first total synthesis of (+)-hyacinthacine A3

Izquierdo, Isidoro; Plaza, Marı́a T.; Franco, Francisco

doi:10.1016/s0957-4166(02)00408-1

Cited by 48 publications

(16 citation statements)

References 18 publications

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“…Izquierdo et al also reported the total synthesis of (+)hyacinthacine A 2 22 and A 3 23 using the similar chemistry to that described above in Schemes 1.1 and 1.2, however starting with 46, the 5-epi-N-Boc analogue of 32 (Scheme 1.3) [37,40]. A Wittig olefination of 33 gave the (E)-α,β-unsaturated aldehyde 34.…”

Section: From 25-dihydroxymethyl-34-dihydroxypyrrolizidines (Dmdp) mentioning

confidence: 99%

“…The interesting biological activities of the pyrrolizidine alkaloids coupled with their polyfunctional and stereochemistry rich nature has attracted the attention of synthetic chemists resulting in the total synthesis of alexine [26,27], and its epimers [26,[28][29][30], australine [21,28,29,31,32] and its epimers [19,20,28,30,31,33,34], casuarine [35,36], and its epimers [24], hyacinthacin A 2 [37][38][39] and A 3 [40], and epimeric hyacinthacines [41,42]. The synthetic routes to these natural products and their analogues can be divided into six distinct groups based either upon a common precursor: (1) carbohydrate; (2) amino acid; or (3) castanospermine; or a common key reaction: (1) cycloaddition; (2) enzymatically catalyzed aldol; or (3) ringclosing metathesis (RCM).…”

Section: Synthetic Studies On 3-hydroxymethylpyrrolizidine Alkaloidsmentioning

confidence: 99%

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The Structure, Biological Activities and Synthesis of 3- Hydroxylpyrrolizidine Alkaloids and Related Compounds

Pyne¹,

Tang

2005

COC

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This review reports on recent developments on the structure, biological activities and synthesis of 3hydroxylpyrrolizidine alkaloids and related compounds.Glycosidase enzymes are involved in a wide range of important biological processes, such as intestinal digestion of carbohydrates, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. Polyhydroxylated alkaloids that mimic the structures of sugars are widespread in plants and have been shown to inhibit glycosidase activities. Some of these compounds show potential as anti-cancer, antiviral and anti-retroviral agents. For example, (-)-swainsonine inhibits Golgi αmannosidase II, an enzyme involved in the processing of glycoproteins on the surface of cancer cells. This process has been associated with cancer metastasis, and thus (-)swainsonine and analogues are potentially useful antimetastasis drugs for the treatment of cancer [1,2]. Unfortunately, (-)-swainsonine is not selective for Golgi αmannosidase II over other α-mannosidases (e.g. lysosomal α-mannosidase) [3] resulting in undesired side effects (e.g. inhibition of the catabolism of oligosaccharides), and thus creating the need for more potent and selective (-)swainsonine analogues.At physiological pH these polyhydroxylated alkaloids are protonated. These protonated compounds are potent glycosidase inhibitors because of their structural resemblance to the oxonium intermediate that is generated in the active site of glycosidase enzymes during the processing of carbohydrates and glycoproteins [4]. For example, the five-membered iminosugar, 2,5-dideoxy-2,5-imino-Daltritol, has two possible half-chair conformers, the 'galacto'-form 1a and the 'manno'-form 1b. Due to the similarities in structures between the two conformers and the galactose oxonium ion 2a and the mannose oxanium ion 2b, respectively, this compound is a strong inhibitor of both αmannosidase and β-1,4-galactosyltransferase [5].These natural products have been classified into five structural classes: polyhydroxylated piperidines (e.g. nojirimycin 3), pyrrolidines (e.g. 2,5-dihydroxymethyl-3,4dihydroxypyrrolidine (DMDP) 4), indolizidines (e.g. swainsonine 5), pyrrolizidines (e.g. australine 6) and nortropanes (e.g. calystegine A 3 7) (Fig. 2). 3-Hydroxymethylpyrrolizidine AlkaloidsAlthough the broad class of pyrrolizidine alkaloids that bear a carbon branch at C-1 (necines) are well documented,

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Section: From 25-dihydroxymethyl-34-dihydroxypyrrolizidines (Dmdp) mentioning

confidence: 99%

Section: Synthetic Studies On 3-hydroxymethylpyrrolizidine Alkaloidsmentioning

confidence: 99%

The Structure, Biological Activities and Synthesis of 3- Hydroxylpyrrolizidine Alkaloids and Related Compounds

Pyne¹,

Tang

2005

COC

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“…[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136] Nevertheless, the strategy also proved to be fruitful in the synthesis of xenovenine and some natural analogues isolated from tropical frogs, [137][138][139][140][141] isoretronecanol, 142 chysine B, 142 austra-line, 143,144 7-epi-alexine, 143 and 7a-epi-7-deoxycasuarine. 145 In few intriguing cases, acetals and ketals instead of the aldehydes or ketones have been employed in a similar fashion.…”

Section: Reductive Aminationmentioning

confidence: 99%

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

Martinez

Belouezzane

Pinto

et al. 2016

Organic Preparations and Procedures International

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“…Pyrrolidine 10 was subjected to the removal of the Cbz group by treatment with catalytic Pd/C (10%) under a hydrogen atmosphere, resulting in a concomitant intramolecular reductive amination and cyclisation (Scheme 2). This type of reaction is well documented starting from the appropriate ketopyrrolidines to afford indolizidine 12 and pyrrolizidine 13 ring systems. Since to the best of our knowledge, there are only a few examples, of seven-membered intramolecular reductive amination steps, the stereochemical outcome was difficult to predict.…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Total synthesis of 275A lehmizidine frog skin alkaloid (or of its enantiomer)

Lesma

Sacchetti

Silvani

2010

Tetrahedron: Asymmetry

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a b s t r a c tA concise asymmetric total synthesis of the potentially bioactive 275A lehmizidine frog skin alkaloid (or of its enantiomer) is described. Key features of the protocol include an acyliminium butenyl Grignard addition and a seven-membered intramolecular reductive amination step. Both reactions ensure a high degree of diastereocontrol, with installation of the same relative configuration at the C3, C5 and C10 stereocentres as in the natural product 275A. Despite this total synthesis, the absolute configuration of the natural product remains unknown, due to the lack of specific rotation data for alkaloid 275A.

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Polyhydroxylated pyrrolizidines. Part 2: The first total synthesis of (+)-hyacinthacine A3

Cited by 48 publications

References 18 publications

The Structure, Biological Activities and Synthesis of 3- Hydroxylpyrrolizidine Alkaloids and Related Compounds

The Structure, Biological Activities and Synthesis of 3- Hydroxylpyrrolizidine Alkaloids and Related Compounds

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

Total synthesis of 275A lehmizidine frog skin alkaloid (or of its enantiomer)

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