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A series of helicid derivatives with benzyl protection of the hydroxyl group at allopyranosyloxy was synthesized and evaluated for sedative-hypnotic activity. The structures of the new compounds were characterized by 1H NMR, IR, and HR-MS spectra. The sedative-hypnotic activities of the target compounds were evaluated using the spontaneous locomotor activity test in mice. Most of the derivatives have moderate to high activity; in particular, compound 3b presented the most potent sedative-hypnotic effect in comparison with the other derivatives, and derivatives 4c, 4d, and 4e also showed higher sedative-hypnotic activities.

This paper reports the synthesis of a new series of helicid–pyrrolidone derivatives (4a–4d, 5a–5d, and 6a–6d), which were tested for antitumor activity against human skov3 cell. In this study, two compounds (4b and 6c) demonstrate high antitumor activity against this cell line having IC50 values of 0.22 and 6.5 μM, respectively, which are lower than those of an inhibitor of heat shock protein 90 (17AAG), currently under clinical evaluation for cancer treatment.

Novel methyl 2-hydroxy-5-substituted benzoate derivatives (2a–2i) were synthesized by esterification of methyl gentisate and long-chain fatty acids. The compounds were structurally confirmed by MS, IR, 1H NMR, and HR-MS spectroscopy. A preliminary bioassay test demonstrated that compounds 2b, 2c, 2f, 2g, 2h showed stronger inhibition of tyrosinase activity. Further pharmacological experiments showed that after substitution modification of compounds 2b, 2f, 2g, and 2h, they have no potential toxicity and phototoxicity.

New 4-chalcone ursolate and 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenyl ursolate derivatives were synthesized by esterification of UA and chalcone or pyrazoline. The compounds were structurally confirmed by IR, 1H NMR, 13C NMR, and HR-MS spectroscopy. The cytotoxicity of ten derivatives was evaluated against A549, SKOV3, and HepG2 cell lines by MTT assay. The result showed that several compounds were more potent than UA against A549 and SKOV3 cells; however, none of them were more potent than UA against HepG2.

Seven helicid derivatives containing decahydroacridine-1,8-dione were prepared via the reactions between 1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione and the corresponding Schiff base. The structures of the helicid derivatives were characterized by IR, 1H NMR, and HR-MS spectrum. The target compounds were evaluated by their hypnotic-sedative activity in vivo. The preliminary bioassay tests showed that some of the compounds had more potent activity than that of helicid.

Reactions of natural helicid with a number of 1,3-dicarbonyl compounds or β-ketoester in the presence of ammonium acetate or 1-naphthylamine gave a series of helicid derivatives containing a 1,4-dihydropyridine fragment (2a–2h). Eight novel helicid derivatives were structurally confirmed by IR, 1H NMR, 13C NMR, and HR-MS spectroscopy and evaluated for their sedative-hypnotic activities on mice. The results demonstrated that two compounds had higher sedative-hypnotic activity compared with helicid.

Under solvent-free conditions, syntheses of 2-aryl-4-(4-β-D-allopyranosyloxyphenyl)-4,6,7,8tetrahydroquinolin-5(1H)-one derivatives were carried out from chalcone (2a–2e), cyclohexane-1,3-dione (3), and NH4OAc in excellent yield without using any catalysts. The structure of the new compounds were characterized by 1H NMR, IR, and HR-MS spectroscopy. The preliminary bioassay tests of 4a–4j indicated that compounds 4b, 4e, and 4f exhibited potent sedative and hypnotic activity.

Using helicid as starting material, E-4-β-D-allopyranoside-cinnamic-4-substituted phenylketones (1a–1h) containing the structure of chalcones were synthesized; then these chalcones were reacted with guanidine hydrochloride through a 1,4-Michael reaction, giving 2-amino-4-(4-β-D-allopyranoside-phenyl)-6-3(4)substituted phenylpyrimidines (2a–2h), which were characterized by IR, 1H NMR, and HR-MS. The target compounds were evaluated by the spontaneous locomotor activity test, showing that all of them had good calming activity; compound 2f was found to have the greatest.

A series of novel helicid derivatives containing 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidine2(1H)-thione moiety (3a–3f and 4a–4f) were synthesized starting from helicid. The structure of the new compounds were characterized by 1H NMR, IR and HR-MS spectra. The sedative-hypnotic activities of the target compounds were evaluated using the test of spontaneous locomotor activity in mice. All of the derivatives produced moderate to high activities; in particular, compound 4a presented the most potent sedative-hypnotic effect in comparison to the other derivatives, and derivatives 3a, 3c, 3d, 3e and 3f also showed potent activities.

5-(4'-β-D-Allopyranosyloxyphenyl)-3-aryl-4,5-dihydropyrazole-1-carbothioamides (2a–2h) were synthesized by the reaction of (1a–1h) with thiosemicarbazide and KOH in ethanol. The structures of all new compounds were characterized by 1HNMR, IR, and MS (HR-MS) spectra. A preliminary bioassay test of 1f–1h and 2a–2h suggested that most of these helicid analogues showed mild to strong activity. Compounds 1g, 2a, 2c, and 2f at a dose of 200 mg·kg–1 were better than that of the parent helicid.

E-(4-β-D-Allopyranosyloxyphenyl)-1-(4-substituted phenyl)propenone derivatives (1a–g) have been synthesized by the Claisen-Schmidt condensation of helicid with 4-substituted acetophenone using 10% NaOH aqueous solution as a catalyst. 6H-2-Amino-4-aryl-6-(4-β-D-allopyranosyloxyphenyl)-1,3-thiazine (2a–g) were synthesized by the 1,4-Michael reaction of 1a–g with thiourea. The structures of all the new products were established by 1H NMR, IR, and MS spectroscopy. Compound 2b (200 mg·kg–1) showed better sedative-hypnotic activity, so further modification of helicid should be worthwhile.