Natural Aryl Glycosides Synthesis: Vanilloloside, Its Analogues and Esters

Session: 
PS1 Poster session 1 Odd numbers
Code: 
P13
Location (hall): 
Foyer
Start/end time: 
Monday, July 1, 2019 - 15:45 to 17:15
David
Avetian

David Avetian1, Elena Stepanova1

1Tomsk Polytechnic University, Tomsk, Russian Federation

The modern trends in drug discovery suggest seeking new therapeutic molecules in traditional medicinal herbs. Aryl glycosides, including vanilloloside 8 (Figure 1), its analogues and derivatives, are common constituents of such plants and have various activity against tumors [1], bacterial [2] and parasitic infections, as well as other useful effects [3]. Their synthesis is preferable over extraction due to many factors such as lability of those molecules during extractions, contamination with other similar compounds and low yields. The developed total synthesis of some aryl glycosides of vanillyl alcohol is presented hereby.

We proposed to synthesize all desired compounds starting from vanillin 1 (Figure 1) and glucose 6. Thus, vanilloloside 8 was synthesized from them in several steps, including ABG synthesis, glycosylation followed by reduction to alcohol 7 and deacetylation. Calleryanin 7a was synthesized analogically from protocatechuic aldehyde 2 prepared from vanillin 1 which was also a starting material for acylation agents 3a and 4 used in the synthesis of 9 and 9a, respectively. To obtain 9b glycoside 7 was treated with commercial benzoyl chloride 5. To conclude, this work presents the first total chemical synthesis of aryl glycosides 8-8a and esters 9-9b.

Figure 1. Synthesis of desired glycosides: (i) — AlCl₃, Py, DCM, Δ, 24 h; (ii) — 1. Py, Pip, malonic acid, 80℃, 4 h, 2. Py, Ac₂O; (iii) — 1. KOH/NaOH/H₂O, 160℃, 2. Py, Ac₂O; (iv) — SOCl₂, 2 h; (v) — 1. Ac₂O, HClO₄, 30–40℃, 2 h, 2. PBr₃, 0–10℃, 3. H₂O, dark, 2 h; (vi) — 1-2, KOH, acetone, 1 h, 2. NaBH₄, H₂O/CHCl₃, CTMAB, 4–5 h; (vii) — MeONa, MeOH, 1 h; (viii) — 3a or 5, Py, DCM, 24 h; (ix) — 4, DCC, DMAP, DCM; (x) — HCl/EtOH/CHCl₃ (1:3:1 vol.), 24–48 h.

Acknowlegements

The work was funded by RFBR according to the research project № 18-33-00365.

References: 
  1. Rayavarapu S, Yarla NS, Kadiri SK, Bishayee A, Vidavalur S, Tadikonda R, et al. Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities. Scientific Reports. 2017;7(1):8309.
  2. Sarıkahya NB, Pekmez M, Arda N, Kayce P, Yavaşoğlu NK, Kırmızıgül S. Isolation and characterization of biologically active glycosides from endemic Cephalaria species in Anatolia. Phytochem. Lett. 2011;4(4):415-420
  3. Abdel-Mageed WM, Backheet EY, Khalifa AA, Ibraheim ZZ, Ross SA. Antiparasitic antioxidant phenylpropanoids and iridoid glycosides from Tecoma mollis. Fitoterapia. 2012;83(3):500-507

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