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Total Synthesis of Natural Hyacinthacine C5, and six Related Hyacinthacine C5 Epimers

Journal Article


Abstract


  • The total synthesis of natural (+)-hyacinthacine C5 was achieved, which allowed correction of its initially proposed structure, as well as six additional hyacinthacine C-type compounds. These compounds were readily accessible from two epimeric anti-1,2-amino alcohols. Keeping a common A-ring configuration, chemical manipulation occurred selectively on the B-ring of the hyacinthacine C-type products through methods of syn-dihydroxylation, SN2 ring-opening of a cyclic sulfate and also employing either (R)- or (R,S)-α-methylallyl amine for the Petasis borono Mannich reaction. Our small analogue library was then assessed for its glycosidase inhibitory potency against a panel of glycosidases. (-)-6-Epi-hyacinthacine C5 and (+)-7-epi-hyacinthacine C5 (compound names are based on the corrected structure of hyacinthacine C5) proved most active, with inhibitory activities ranging between weak (IC50 = 130 μM) to moderate (IC50 = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase and sucrase, thus identifying potential new leads for future antidiabetic drug development.

UOW Authors


  •   Carroll, Anthony (external author)
  •   Savaspun, Kongdech (external author)
  •   Willis, Anthony C. (external author)
  •   Hoshino, Masako (external author)
  •   Kato, Atsushi (external author)
  •   Pyne, Stephen

Publication Date


  • 2018

Citation


  • Carroll, A. W., Savaspun, K., Willis, A. C., Hoshino, M., Kato, A. & Pyne, S. G. (2018). Total Synthesis of Natural Hyacinthacine C5, and six Related Hyacinthacine C5 Epimers. Journal of Organic Chemistry, 83 (10), 5558-5576.

Scopus Eid


  • 2-s2.0-85046532539

Number Of Pages


  • 18

Start Page


  • 5558

End Page


  • 5576

Volume


  • 83

Issue


  • 10

Place Of Publication


  • United States

Abstract


  • The total synthesis of natural (+)-hyacinthacine C5 was achieved, which allowed correction of its initially proposed structure, as well as six additional hyacinthacine C-type compounds. These compounds were readily accessible from two epimeric anti-1,2-amino alcohols. Keeping a common A-ring configuration, chemical manipulation occurred selectively on the B-ring of the hyacinthacine C-type products through methods of syn-dihydroxylation, SN2 ring-opening of a cyclic sulfate and also employing either (R)- or (R,S)-α-methylallyl amine for the Petasis borono Mannich reaction. Our small analogue library was then assessed for its glycosidase inhibitory potency against a panel of glycosidases. (-)-6-Epi-hyacinthacine C5 and (+)-7-epi-hyacinthacine C5 (compound names are based on the corrected structure of hyacinthacine C5) proved most active, with inhibitory activities ranging between weak (IC50 = 130 μM) to moderate (IC50 = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase and sucrase, thus identifying potential new leads for future antidiabetic drug development.

UOW Authors


  •   Carroll, Anthony (external author)
  •   Savaspun, Kongdech (external author)
  •   Willis, Anthony C. (external author)
  •   Hoshino, Masako (external author)
  •   Kato, Atsushi (external author)
  •   Pyne, Stephen

Publication Date


  • 2018

Citation


  • Carroll, A. W., Savaspun, K., Willis, A. C., Hoshino, M., Kato, A. & Pyne, S. G. (2018). Total Synthesis of Natural Hyacinthacine C5, and six Related Hyacinthacine C5 Epimers. Journal of Organic Chemistry, 83 (10), 5558-5576.

Scopus Eid


  • 2-s2.0-85046532539

Number Of Pages


  • 18

Start Page


  • 5558

End Page


  • 5576

Volume


  • 83

Issue


  • 10

Place Of Publication


  • United States