•Short synthesis of calceolarioside-B and eutigoside-A.•General route applicable to the synthesis of PhGs acylated at O-6.•Acylation at O-6 is selective.•No protection/deprotection steps.A convenient 4-step synthesis of calceolarioside-B 1 and eutigoside-A 2 in high overall yield is described. The key step involved the regioselective, Me2SnCl2-catalyzed O-6 acylation of unprotected 2-phenylethyl-β-d-glucosides 5a–b with cinnamoyl chlorides 6a–b in excellent yields. Acylation at O-6 is selective with the acid chlorides used. This work serves as a model for the convenient synthesis of phenylpropanoid glycosides acylated at O-6.

A convenient synthesis of phenylpropanoid glycoside osmanthuside-B6 is disclosed. The key steps involved regioselective coumaroylation and rhamnosylation of unprotected phenylethyl-β-D-glucopyranoside to give 2- and 3-O-rhamnosyl orthoester glucopyranosides. Rearrangement of these orthoesters followed by selective removal of their acetyl and allyl groups gave osmanthuside-B6 in 22% overall yield. The rearrangement involved a newly discovered glucose–rhamnose orthoester double isomerization process that has the potential to provide a convenient access to many complex phenylpropanoid glycosides. The synthetic route developed is envisioned to serve as a model for the preparation of phenylpropanoid glucosides having a (substituted) cinnamoyl moiety at O-6 and a saccharide moiety at O-3.

A short synthesis of phenylethyl glycosides grayanoside-A 1, 2 and analogues 3–4 in high 43–65% overall yields is described. The main synthetic step involved regioselective O-6 acylation of unprotected 2-phenylethyl-β-D-glucoside 7 with cinnamoyl chlorides 8a-d using Me2SnCl2 as catalyst. The acylation at O-6 is regioselective regardless of the type of cinnamoyl chloride used. Protection/deprotection steps of the glucoside core were not necessary. The synthetic route is generally applicable for the synthesis of phenylpropanoid glycoside class of compounds acylated at O-6.

•Fish oil was encapsulated using hydrophobic N-stearoyl O-butylglyceryl chitosan.•Microencapsulation using membrane & ultrasonic emulsifications were compared.•Microcapsules showed sustained release oil and profile depended on the process.•Encapsulation impeded heat transfer and increased thermal stability of the fish oil.Fish oil-loaded microcapsules were prepared from oil-in-water emulsions using N-stearoyl O-butylglyceryl chitosan as shell material. The emulsions were prepared by both membrane and ultrasonic emulsification processes under variable conditions to examine the effect of the emulsification process and encapsulation conditions on the characteristics of the microcapsules. The microcapsules were characterized with respect to their morphologies, colloidal stability, loading capacity, encapsulation efficiency and release profile. The microcapsules formed by the membrane emulsification process exhibited larger diameter compared to those from the ultrasonic emulsification process which gave a mean effective diameter of ≈1 μm. The microcapsules obtained by membrane emulsification process gave better loading capacity and encapsulation efficiency. The microcapsules from both processes showed sustained release of fish oil and the release profile depended on the type of the process. TGA confirmed that encapsulation using N-stearoyl O-butylglyceryl chitosan impeded heat transfer and significantly increased the thermal stability of the encapsulated fish oil.

Phenylpropanoid sucrose esters are important class of plant-derived natural products and have greater potential to be leads for new drugs because of their structural diversity and broad-array of pharmacological and biological activities. Regio- and chemo-selective acylation of 2,1′:4,6-O-di-isopropylidene sucrose 4 with cinnamoyl chloride 5 and p-acetoxycinnamoyl chloride 6 afforded mono-, di-, tri- and tetra- variant PSEs in moderate yields. The first total synthesis of di-substituted PSE, lapathoside D 1′ has been achieved successfully in short and simple synthetic steps from sucrose 3 as an inexpensive starting material. Lapathoside D 1 and a set of selected synthesized PSEs were tested for in vitro cytotoxicity against human cervical epithelioid carcinoma (HeLa) cell lines. Most of the compounds exhibited significant antitumor activity with their IC50 values ranging from 0.05 to 7.63 μM. The primary screening results indicated that PSEs might be valuable source for new potent anticancer drug candidates.Graphical abstractA series of phenylpropanoid sucrose esters, lapathoside D and its analogs were successfully synthesized in short and simple synthetic route from sucrose and evaluated for their antitumor activity against human cervical epithelioid carcinoma cells. The preliminary results indicated that PSEs might be valuable source for new potent anticancer drug candidates.Highlights► First total syntheses of Lapathoside D along with 17 unnatural PSEs. ► Significant antitumor activity with their IC50 values ranging from 0.05 to 7.63 μM. ► Di-O-isopropylidene and acetyl groups contribute significantly to cytotoxic activity. ► PSEs are potential source for new potent anticancer drug candidates.

The first total synthesis of natural phenylpropanoid sucrose esters (PSEs) helonioside A 1, 3′,4′,6′-tri-O-feruloylsucrose 2 and lapathoside C 3 along with 17 unnatural PSE analogs has been successfully accomplished in a short and simple synthetic route. A selected set of 17 synthesized PSEs were evaluated for the antiproliferative activity against human cervical epithelioid carcinoma (HeLa) cell lines using MTS assay method. Eleven (11) compounds showed significant antiproliferative activity with their IC50values ranging from 0.16 to 6.01 μM. The structure–activity-relationship studies revealed that the antiproliferative activity is influenced by the lipophilicity and number of feruloyl substituents on these compounds. The preliminary screening indicated that these compounds are potentially very valuable source for new lead chemotherapeutics.Graphical abstractHelonioside A, 3′,4′,6′-tri-O-feruloylsucrose, lapathoside C and their unnatural analogs were successfully synthesized through a simple route. They were evaluated for their antiproliferative activity against human cervical epithelioid carcinoma cell lines. The preliminary screening results indicated that these compounds are potentially valuable source for new lead chemotherapeutics.Highlights► First synthesis of helonioside A, 3′,4′,6′-tri-O-feruloylsucrose, lapathoside C. ► Synthesis of 17 unnatural PSEs. ► Significant antiproliferative activity (IC50 = 0.16 μM) against HeLa cell lines. ► Lipophilicity and number of feruloyl substituents affect the activity.

An efficient catalytic system comprising of chiral C1-tetrahydro-1,1′-bisisoquinoline and CuCl in the ratio of 2:1 has been developed for the enantioselective Henry reaction. The catalytic efficiencies of the chiral C1-tetrahydro-1,1′-bisisoquinolines are governed to a great extent by the structural constraints and the type of substituent on the sp3-N. Aromatic and aliphatic aldehydes reacted with nitromethane to give β-nitroalcohols in very high yields (up to 95%) and enantioselectivities (up to 91% ee). The present catalyst system is simple in operation since no special precautions were taken to exclude moisture or air from the reaction flask and no additives were required for activation. Nonlinear effects have also been studied for this reaction.(R)-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC18H16N2[α]D20=+202.0 (c 0.9, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (R)

Chiral complex derived from N-methyl-C1-tetrahydro-1,1′-bisisoquinolines (R)-1b and Cu(I)Cl promoted the diastereoselective Henry reaction of nitroethane with a series of aromatic and aliphatic aldehydes. The nitroalcohol adducts were obtained in excellent yields (up to 95%), moderate anti-selectivity (up to 2.6:1), and good enantioselectivity (up to 92% ee) without any special precautions to exclude moisture or air.(R)-N′-Methyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC19H18N2[α]D25=+159.7 (c 1.13, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (R)

New highly constrained chiral C1-1,1′-bisisoquinoline ligands have been synthesized. X-ray crystallographic analysis of these ligands showed peculiar structural differences between the parent 1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline and its alkyl, acyl and sulfonyl derivatives. The consequences of their geometrical conformations on enantioinduction were examined by employing the enantioselective addition of diethylzinc to aldehydes. Such conformations greatly affected the catalytic efficiency of these ligands.Figure optionsDownload full-size imageDownload as PowerPoint slide(+)-1′,2′,3′,4′-Tetrahydro-1,1′-bisisoquinolineC18H16N2[α]D25=+202.0 (c 0.90, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate(+)-N′-Methyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC19H18N2[α]D25=+159.7 (c 1.13, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate(+)-N′-(2-Hydro-5-nitro-benzyl)-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC25H21N3O3[α]D25=+62.5 (c 0.77, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate(+)-N′-Ethanoyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC20H18N2O[α]D25=+399.4 (c 0.65, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate(+)-N′-Tosyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC25H22N2O2S[α]D25=+243.5 (c 1.0, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate

2,4,6-Trimethylphenol was selectively oxidized to 3,5-dimethyl-4-hydroxybenzaldehyde in very good yields using catalytic or equivalent amounts of CuCl2 in the presence of K2CO3 and H2O2 in i-PrOH at 65 °C. The effect of the molar ratios of CuCl2, K2CO3 and H2O2 on the yields and product distribution was examined. The oxidation reaction was found to proceed smoothly without the use of additives or ligands which were reported to be necessary.Download full-size image

A convenient synthesis of phenylpropanoid glycoside osmanthuside-B6 is disclosed. The key steps involved regioselective coumaroylation and rhamnosylation of unprotected phenylethyl-β-D-glucopyranoside to give 2- and 3-O-rhamnosyl orthoester glucopyranosides. Rearrangement of these orthoesters followed by selective removal of their acetyl and allyl groups gave osmanthuside-B6 in 22% overall yield. The rearrangement involved a newly discovered glucose–rhamnose orthoester double isomerization process that has the potential to provide a convenient access to many complex phenylpropanoid glycosides. The synthetic route developed is envisioned to serve as a model for the preparation of phenylpropanoid glucosides having a (substituted) cinnamoyl moiety at O-6 and a saccharide moiety at O-3.