Total synthesis of the natural product EBC-329.

The first total synthesis of an anti-leukemic diterpene natural product EBC-329 (1) has been accomplished starting from readily available 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (7). An efficient and general approach has been reported for the synthesis of EBC-329 in 13 steps with an overall yield of 10%.

A study of anhydrocelluloses--is a cellulose structure with residues in a 1C4-conformation more prone to hydrolysis?

A study of the effect of introduction of 3,6-anhydroglucose residues in the cellulose structure on glycoside hydrolysis rate was performed. A cellotetrose with an 3,6-anhydroglucose as the third residue was synthesised. Acidic hydrolysis of this tetrasaccharide showed that hydrolysis of the 3,6-anhydro-ß-D-glucoside linkage was 31.400 times faster than hydrolysis of cellobiose. A series of different 3,6-anhydrocelluloses with different degree of substitution were prepared by tosylation of cellulose with varying amounts of tosyl chloride in dimethylacetamide and subsequent treatment with sodium hydroxide. Anhydrocelluloses with degrees of substitution of 0.02, 0.07, 0.31 and 0.74 were obtained. The anhydrocelluloses were subjected to acidic hydrolysis in 2.0 M aqueous HCl and the rate of hydrolysis monitored by ion chromatography analysis of the amount of glucose and/or cellobiose formed. All 3,6-anhydrocelluloses hydrolyzed with a faster rate than cellulose, but the anhydrocellulose with a low degree of substitution (ds = 0.07) hydrolyzed fastest which was 90 times faster than cellulose.

Synthesis and conformational study of chiral oxepines: the Baylis-Hillman reaction and RCM approach with sugar aldehyde.

The Baylis-Hillman reaction of 3-O-allyl-alpha-d-xylo-pentodialdo-1,4-furanose 3 afforded a diastereomeric mixture of d-gluco- and l-ido-configured alpha-methylene-beta-hydroxy esters 4a and 4b, respectively, in a ratio of 2:3. Reduction of the ester functionality in 4a/4b gave alcohols 5a/5b. The diene thus formed in 5a/5b was subjected to ring-closing metathesis (Grubbs' second-generation catalyst) to afford oxa-bicyclic ring system 6a/6b in high yield. Further manipulation of the acetonide functionality in 6a and 6b afforded new polyhydroxylated oxepines 1a/2a and 1b/2b, respectively. The (1)H NMR of oxepines 1a and 1b in D(2)O showed doubling of signals indicating their existence in two different rotamers/conformers. This fact was substantiated by calculating energetics of 1 and 2 conformers using the density functional theory and correlating the calculated (1)H NMR chemical shift pattern with that of the experimental spectra.

Multifunctional inulin tethered silver-graphene quantum dots nanotheranostic module for pancreatic cancer therapy.

Cancer nanotechnology is an emerging area of cancer diagnosis and therapy. Although considerable progress has been made for targeted drug delivery systems to deliver anticancer agents to particular site of interest, new nanomaterials are frequently being developed and explored for better drug delivery efficiency. In the present work, we have explored a novel nanoformulation based on silver-graphene quantum dots (Ag-GQDs) nanocomposite for its successful implementation for pancreatic cancer specific drug delivery in wistar rats. Carboxymethyl inulin (CMI); a modified variant of natural polysaccharide inulin is tethered with the nanocomposite via carbodiimide coupling to enhance the biocompatibility of nanoformulation. Experiments are performed to investigate the cytotoxicity reduction of silver nanoparticles after inulin tethering as well as anticancer efficacy of the system using 5-Fluorouracil (5-FU) as model drug. SEM, TEM, FT-IR, UV-vis, photoluminescence and anti proliferative assays (MTT) are performed for characterisation of the nanocomposite. Hyaluronic acid (HA) is conjugated as targeting moiety for CD-44 (cancer stem cell marker) to fabricate a complete targeted drug delivery vehicle specific for pancreatic cancer. In the present work two prime objectives were achieved; mitigation the toxicity of silver nanoparticles by inulin coating and it's in vivo application for pancreatic cancer.