Synthesis of Pentahydroxylated Pyrrolizidines and Indolizidines

Tamayo, Juan A.; Franco, Francisco; Re, Daniele Lo; Sánchez-Cantalejo, Fernando

doi:10.1021/jo900801c

Cited by 33 publications

(8 citation statements)

References 57 publications

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“…Our groups have a longstanding interest in the total synthesis of pyrrolizidine and indolizidine alkaloids and analogues 6,7. In particular, Goti and co‐workers have widely exploited the use of polyhydroxylated nitrones as dipoles in 1,3‐dipolar cycloaddition chemistry6a,6b,4e and as electrophiles towards organometallics,6c,6d whereas Tamayo and co‐workers have recently expanded the scope of cycloadditions for the synthesis of unnatural pentahydroxypyrrolizidines and ‐indolizidines with hydroxymethyl groups at C5 by use of chemoenzymatically prepared but‐3‐ene‐1,2‐diol derivatives as dipolarophiles 8…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Glycosidase Inhibition Studies of 5‐Methyl‐Substituted Tetrahydroxyindolizidines and ‐pyrrolizidines Related to Natural Hyacinthacines B

et al. 2013

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Keywords: Total synthesis / Azasugars / Alkaloids / Enzyme catalysis / Inhibitors / CycloadditionThe synthesis of three tetrahydroxyindolizidines and one tetrahydroxypyrrolizidine related to natural hyacinthacines B and their biological evaluation as glycosidase inhibitors is reported. The target molecules were obtained through highly stereoselective cycloadditions between sugriched allylic and homoallylic alcohols. This allowed the installation of a methyl group at C5 -a common feature of many natural hyacinthacines -with high control over the stereoselectivity. The new

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Section: Introductionmentioning

confidence: 99%

Synthesis and Glycosidase Inhibition Studies of 5‐Methyl‐Substituted Tetrahydroxyindolizidines and ‐pyrrolizidines Related to Natural Hyacinthacines B

et al. 2013

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“…The first total synthesis of hyacinthacine C 2 and proposed structure of C 3 and their C5 epimers 10 and 11, respectively by Yoda et al [60] Scheme 2. The total synthesis of unnatural hyacinthacine C 2/3 analogues 20 and 24 by Tamayo et al [71]…”

Section: Tamayo Et Al 2010mentioning

confidence: 99%

“…At around the same time as Yoda et al , Tamayo and co-workers published their work detailing the synthetic approach to making analogues of hyacinthacines C 2 / 3 from the arabinose derived nitrone 12 [ 71 ] (Scheme 2 ). Their synthesis began with the 1,3-dipolar cycloaddition of the chemoenzymatically prepared 3-buten-1,2-diol derivatives 13a or 13b to nitrone 12 to afford cycloadducts 14 or 15 , respectively.…”

Section: Hyacinthacine Alkaloidsmentioning

confidence: 99%

The History of the Glycosidase Inhibiting Hyacinthacine C-type Alkaloids: From Discovery to Synthesis.

Carroll

Pyne

2019

COS

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Background: The inherent glycosidase inhibitory activity and potentially therapeutic value of the polyhydroxylated pyrrolizidine alkaloids containing a hydroxymethyl substituent at the C-3 position have been well documented. Belonging to this class, the naturally occurring hyacinthacine C-type alkaloids are of general interest among iminosugar researchers. Their selective micromolar α -glycosidase inhibitory ranges (10 – 100 μM) suggest that these azasugars are potential leads for treating type II diabetes. However, the structures of hyacinthacine C1, C3 and C4 are insecure with hyacinthacine C5 being recently corrected. Objective: This review presents the hyacinthacine C-type alkaloids: their first discovery to the most recent advancements on the structures, biological activities and total synthesis. Conclusion: The hyacinthacine C-type alkaloids are of exponentially increasing interest and will undoubtedly continue to be reported as synthetic targets. They represent a challenging but rewarding synthetic feat for the community of those interested in accessing biologically active iminosugars. Since 2009, ten total syntheses have been employed towards accessing similarly related products but only three have assessed the glycosidase inhibitory activity of the final products. This suggests the need for an accessible and universal glycosidase inhibitory assay so to accurately determine the structure-activity relationship of how the hyacinthacine C-type alkaloids inhibit specific glycosidases. Confirming the correct structures of the hyacinthacine C-type alkaloids as well as accessing various analogues continues to strengthen the foundation towards a marketable treatment for type II diabetes and other glycosidase related illnesses.

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“…The authors showed that lipase-mediated resolution was effective for the Hyacinthacine C 2/3 analogues were prepared by nitrone cycloaddition of 402 with allylic alcohol 468 (/ 466, Scheme 71) or allylic acetate 469 (en route to 470). 164 The dipolarophiles were obtained by lipase mediated kinetic resolution of racemic 3-buten-1,2-diol and their cycloadditions found to afford predominantly one diastereromer in each case. From isoxazolidine 466, a standard sequence was followed (sulfonylation, N-O reduction and cyclisation, then two deprotection steps) to give pyrrolizidine 467.…”

Section: Hyacinthacinesmentioning

confidence: 99%