Stereoselective synthesis and biological evaluation of d-fagomine, d-3-epi-fagomine and d-3,4-epi-fagomine analogs from d-glyceraldehyde acetonide as a common building block

Abstract

The stereoselective synthesis of D-fagomine, D-3-epi-fagomine, and D-3-epi-fagomine analogs starting from readily available D-glyceraldehyde acetonide has been achieved. The synthesis involves diastereoselective anti-vinylation of its homoallylimine, ring-closing metathesis, and stereoselective epoxidation followed by regioselective ring-opening or stereoselective dihydroxylation. The lack of a strong activity as glycosidase inhibitors of these compounds could be advantageous for their therapeutic use as chaperones.

Triple‐Helix‐Stabilizing Effects in Collagen Model Peptides Containing PPII‐Helix‐Preorganized Diproline Modules

“…Its conversion into Fmoc‐ H 2 ‐ProM1 ‐OH then proceeded smoothly under the standard conditions. While other reagents, such as MCPBA, gave unsatisfactory results, epoxidation of the C=C double bond of Boc‐ ProM1 ‐O t Bu was achieved by dioxirane generated in situ from oxone® and trifluoroacetone at 15 °C . Noteworthy, the α‐epoxide (Boc‐ ep‐ProM1 ‐O t Bu) was obtained as a single diastereomer.…”

Recent advances in the total synthesis of polyhydroxylated alkaloids via chiral oxazines

“…In summary, our synthetic strategy utilizing syn , syn -, syn , anti -, anti , syn -oxazines as chiral building blocks enabled the synthesis of 30 diverse polyhydroxylated alkaloids, providing enantiomerically and diastereomerically pure products in a facile, efficient, and versatile manner. Various flexible strategies employed by other researchers, utilizing such as Overman rearrangement reaction, 38–42 tandem [4 + 2]/[3 + 2] nitroalkene cycloaddition, 45–49 Birch reduction, 50–54 and metal-mediated cross-coupling, 81–83 or with the use of key starting materials like chlorosulfonyl isocyanate, 61–67 Garner's aldehyde, 71–80 protected amino aldehydes, 84,85 and sugar-derived cyclic nitrone, 55–60,86–91 have been valuable. However, our strategy stands out due to its versatility, successfully synthesizing a range of natural products and offering potential applications in other natural products and pharmaceuticals like lycoricidine and miglitol.…”

“…Nash et al not only detailed sophisticated synthetic methods but also conducted bioassays to evaluate their glycosidase inhibitory activities. Their endeavors included compounds such as 1-deoxygalactonojirimycin, 77 fagomine, 78 castanospermine, 79 1-epi-castanospermine, 79 7-epi-australine, 79 and 3-epi-casuarine. 79,80 Py and colleagues proposed the use of SmI 2 -mediated crosscoupling of nitrones with β-silyl-α,β-unsaturated esters for the synthesis of bicyclic cores.…”

“…Nash et al not only detailed sophisticated synthetic methods but also conducted bioassays to evaluate their glycosidase inhibitory activities. Their endeavors included compounds such as 1-deoxygalactonojirimycin, 77 fagomine, 78 castanospermine, 79 1- epi -castanospermine, 79 7- epi -australine, 79 and 3- epi -casuarine. 79,80…”

Triple‐Helix‐Stabilizing Effects in Collagen Model Peptides Containing PPII‐Helix‐Preorganized Diproline Modules

“…Its conversion into Fmoc-H 2 -ProM1-OH then proceeded smoothly under the standard conditions.W hile other reagents,s uch as MCPBA, gave unsatisfactory results,e poxidation of the C=Cd ouble bond of Boc-ProM1-OtBu was achieved by dioxirane generated in situ from oxone and trifluoroacetone at 15 8 8C. [31] Noteworthy,the a-epoxide (Bocep-ProM1-OtBu) was obtained as asingle diastereomer.T he configuration was assigned through NOE NMR experiments and confirmed by crystal-structure analysis (Figure 3). Because of the sensitivity of the epoxide function, triisoproylsilane was added during TFAt reatment in the preparation of Fmoc-ep-ProM1-OH.…”