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

Journal Article


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Abstract


  • 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.

UOW Authors


Publication Date


  • 2019

Citation


  • Carroll, A. & Pyne, S. G. (2019). The History of the Glycosidase Inhibiting Hyacinthacine C-type Alkaloids: From Discovery to Synthesis. Current Organic Synthesis, 16 498-522.

Scopus Eid


  • 2-s2.0-85070550654

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1808&context=smhpapers1

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/794

Number Of Pages


  • 24

Start Page


  • 498

End Page


  • 522

Volume


  • 16

Place Of Publication


  • United Arab Emirates

Abstract


  • 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.

UOW Authors


Publication Date


  • 2019

Citation


  • Carroll, A. & Pyne, S. G. (2019). The History of the Glycosidase Inhibiting Hyacinthacine C-type Alkaloids: From Discovery to Synthesis. Current Organic Synthesis, 16 498-522.

Scopus Eid


  • 2-s2.0-85070550654

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1808&context=smhpapers1

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/794

Number Of Pages


  • 24

Start Page


  • 498

End Page


  • 522

Volume


  • 16

Place Of Publication


  • United Arab Emirates