Concise synthesis of (−)-steviamine and analogues and their glycosidase inhibitory activities

Abstract

A concise synthesis of (−)-steviamine is reported along with the synthesis of its analogues 10-nor-steviamine, 10-nor-ent-steviamine and 5-epi-ent-steviamine. These compounds were tested against twelve glycosidases (at 143 μg mL−1 concentrations) and were found to have in general poor inhibitory activity against most enzymes. The 10-nor analogues however, showed 50-54% inhibition of α-L-rhamnosidase from Penicillium decumbens while one of these, 10-nor-steviamine, showed 51% inhibition of N-acetyl-β-D-glucosaminidase (from Jack bean) at the same concentration (760 μM). A concise synthesis of steviamine is reported along with the synthesis of its analogues 10-nor-steviamine, 10-nor-ent-steviamine and 5-epi-ent-steviamine. These compounds were tested against twelve glycosidases (at 143 g/mL concentrations) and were found to have in general poor inhibitory activity against most enzymes. The 10-nor analogues however, showed 50-54% inhibition of -L-rhamnosidase from Penicillium decumbens while one of these, 10-nor-steviamine, showed 51% inhibition of N-acetyl--D-glucosaminidase (from Jack bean) at the same concentration (760 M).

Direct synthesis of imino-C-nucleoside analogues and other biologically active iminosugars

“…Figure 5 highlights the further application of this convenient strategy to the rapid preparation of several structurally complex polyhydroxy indolizidine and pyrrolizidine alkaloids, including analogues of the glycosidase inhibitors hyacinthacine and steviamine. While several strategies could be exploited for the second annulation event, ready access to the N -allyl pyrrolidine 40 , alkyl chloride 33 and protected ketones 34 and 35 suggested annulation events involving ring closing metathesis 38 39 , alkylation 24 40 41 or reductive amination 17 42 . For example, heating the dienylpyrrolidine 40 with the Hoveyda–Grubbs 2nd generation catalyst 43 in toluene provided the unsaturated indolizidine 45 in excellent overall yield from 4-pentenal ( 44 ).…”

Stereoselective Synthesis of Ribofuranoid exo-Glycals by One-Pot Julia Olefination Using Ribofuranosyl Sulfones

“…7 was synthesized according to the β-selective ribofuranosylation reported by Hocek et al 6 (0.661 g, 2.00 mmol) and 2-mercaptobenzothiazole (0.502 g, 3.00 mmol) were dried by repeated coevaporation with dry MeCN (5 × 5 mL) and dissolved in dry MeCN (2.00 mL). The solution was cooled to 0 °C, before dry i -Pr 2 NEt (0.523 mL, 3.00 mmol), diisopropyl azodicarboxylate (DIAD, 0.827 mL, 4.20 mmol), and Bu 3 P (0.989 mL, 4.00 mmol) were added under stirring, and stirring was continued overnight at rt.…”

First total synthesis of kipukasin A

“…[α] D 25 +133.3 ( c 0.1, acetone) (lit. [37] [α] D 25 +125.9 ( c 1.1, CHCl 3 )); 1 H NMR (400 MHz, DMSO- d 6 ) δ 5.81 (d, J = 3.7 Hz, 1H), 4.77 (t, J = 4.2 Hz, 1H), 4.67 (dd, J = 9.1, 4.8 Hz, 1H), 4.24 (dd, J = 12.1, 2.7 Hz, 1H), 4.20–4.15 (m, 1H), 4.05 (dd, J = 12.1, 5.4 Hz, 1H), 2.07 (s, 3H), 2.03 (s, 3H), 1.45 (s, 3H), 1.27 (s, 3H); 13 C NMR (101 MHz, DMSO- d 6 ) δ 170.1, 169.7, 112.2, 103.9, 76.8, 75.1, 71.9, 62.4, 26.4, 20.5, 20.4; LRMS (ESI) m/z : 297.2 [M + Na] + ; HRMS (ESI) m/z : [M + Na] + calcd for C 12 H 18 O 7 Na, 297.0945; found, 297.0943.…”