Synthesis of Glucoconjugates of Echinochrome Derivatives
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SYNTHESIS OF GLUCOCONJUGATES OF ECHINOCHROME DERIVATIVES
N. D. Pokhilo, L. N. Atopkina,* and N. K. Utkina
Previously, water-soluble quinone–carbohydrate conjugates that were not glycosides because the naphthoquinoid and carbohydrate fragments were bound through an ether bond were synthesized by us. The obtained conjugates exhibited cytotoxic activity against tumor cells, induced their apoptosis, and possessed contraceptive and antioxidant properties [1–5]. We continued this research with the goal of synthesizing glucoconjugates of echinochrome, a metabolite of the sand dollar Scaphechinus mirabilis. Attempted ether exchange of echinochrome trimethyl ether (5,8-dihydroxy-2,3,6-trimethoxy-7-ethyl-1,4naphthoquinone, 1) with 1,2-O-isopropylidene-α-D-glucofuranose (2) in the presence of MeONa in MeOH formed a complicated inseparable product mixture. OH 8
R4
O
OH 1
8a
8'
R1
OH
O 1'
8'a
O
7'
6
5
4'a
R3
6
4a
OH
4
R2
Cl
O
OH
1, 3, 7 - 10
OMe
4'
5'
OH O OH 3
O O
OMe
1
O OH
O Cl
O
O
O
O OH
O
OH
4
5 OH
1: R1 = R2 = R3 = OMe, R4 = Et 3: R1 = R2 = OMe, R3 = Cl, R4 = Et 7: R1 = OH, R2 = Et, R3 = R4 = OMe 8: R1 = OMe, R2 = OH, R3 = Cl, R4 = Et 9: R1 = OH, R2 = OMe, R3 = Cl, R4 = Et 10: R1 = OMe, R2 = H, R3 = Et, R4 = Cl
O O
O OMe
O OH O OH
OMe OH
O
6
Conjugates of echinochrome derivatives were prepared using 5,8-dihydroxy-2,3-dimethoxy-6-chloro-7-ethyl-1,4naphthoquinone (3) [6], a side product of incomplete substitution of trichloroethylnaphthazarin in the synthesis of echinochrome trimethyl ether. Reaction of 3 (90 mg, 0.29 mmol) with carbohydrate 2 (630 mg, 2.9 mmol) in DMSO (9 mL) in the presence of several drops of saturated MeONa solution in MeOH at 90°C for 3 h according to the published method [5] gave the expected transetherification products 4 and 5 as an inseparable mixture (25 mg, 2:1, 21%) and the product from substitution of the Cl by 2 (6, 16 mg, 14%). Also, the reaction was accompanied by formation of hydrolysis products 7–9 (11 mg, 2.5:1.5:1, 16%), which was confirmed by storing 3 under the reaction conditions without adding 2. The course of reactions and purity of products were monitored by TLC on Sorbfil plates (Russia) using hexane–Me2CO (2:1 and 3:2). Reaction products were separated by preparative TLC (hexane–Me2CO, 3:1) on KSK silica gel (170 mesh). The structures of 4–9 were elucidated using IR, PMR, 13C NMR, and 2D spectroscopy (COSY, HSQC, HMBC) and multiplicities of 13C resonances in DEPT-135 experiments. The PMR spectrum of the mixture of 4 and 5 showed a set of two groups of resonances, i.e., two pairs of resonances for the α-OH protons (δ 12.75 and 13.05 ppm) and (δ 12.94 and 12.84 ppm) in a 2:1 ratio of integrated intensities; two resonances for methoxyls (δ 4.17 and 4.18 ppm, 2:1); and two overlapping resonances for CH3CH2 protons as quartets of different intensities (δ 2.91 and 2.92 ppm, 2:1), etc. The 13C NMR spectrum also displayed a set of two groups of resonances G. B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russia
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