Influence of hydrophilic polymers on mechanical property and wound recovery of hybrid bilayer wound dressing system for delivering thermally unstable probiotic.

In this study, a novel hybrid bilayer wound dressing (HBD) has been developed for delivering a thermally unstable probiotic, Lactobacillus brevis. The HBD was composed of two layer, a hydrocolloid layer and a Lactobacillus brevis-loaded hydrogel layer as a block supporter and drug carrier, respectively. Moreover, various probiotic-loaded hydrogel layers in HBD were prepared with polyvinyl alcohol (PVA) and numerous hydrophilic polymers via a freezing and thawing method, and their mechanical property, release and wound recovery were assessed. Among the hydrophilic polymers investigated, copovidone most improved the mechanical strength, swelling ability, and release properties; and thus, copovidone/PVA (ratio of 1.0/10) was determined as an appropriate composition of hydrogel layer in HBD. The selected HBD exhibited superior stability than conventional dressing, maintaining approximately 90% of Lactobacillus brevis (9.0 × 108 CFU) during the preparation and storage process. Moreover, the HBD had about 5- and 4-fold better swelling ability and elasticity compared to the conventional dressing. Additionally, it exhibited superior recovery efficacy than the commercial dressing in the animal study. Therefore, this HBD system for delivering a thermally unstable Lactobacillus brevis would be a promising wound dressing with excellent mechanical property and wound recovery.

Diastereoselective Construction of trans-2-Alkyl-6-aryl-3,6-dihydro-2H-pyrans via Dehydrogenative Cycloetherification Promoted by DDQ.

A diastereoselective synthesis of trans-2-alkyl-6-aryl-3,6-dihydro-2H-pyrans has been described. Dehydrogenative cycloetherification of (E)-(±)-1-aryl-5-hydroxy-1-alkenes promoted by DDQ proceeded cleanly via 6-endo cyclization to afford trans-2-alkyl-6-aryl-3,6-dihydro-2H-pyrans (32 examples) in good yield (up to 89%) and with moderate to excellent diastereoselectivity (up to 99:1). The synthetic utility of the method was illustrated by the second total synthesis of (±)-(2R,6S)-3,4-dehydro-1,7-bis(4-hydroxy phenyl)-4'-de-O-methyl centrolobine and a total synthesis of (±)-centrolobine.

Direct and Efficient C(sp3)-H Functionalization of N-Acyl/Sulfonyl Tetrahydroisoquinolines (THIQs) With Electron-Rich Nucleophiles via 2,3-Dichloro-5,6-Dicyano-1,4-Benzoquinone (DDQ) Oxidation.

A highly efficient metal-free oxidative direct C(sp3)-H functionalization of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) with a wide range of electron-rich nucleophiles was accomplished under mild conditions through oxidation with DDQ and subsequent trapping of the resulting reactive and stable N-acyl/sulfonyl iminium ions. The synthetic utility of this method was illustrated by a concise and efficient total synthesis of (±)-benzo[a]quinolizidine (10) in 3 steps from the known N-Cbz 1,2,3,4-THIQ 4b.

Lewis Acid-Promoted Regio- and Diastereoselective Cross-Coupling of Aryl-Substituted 1,2-Diols and Boronic Acids.

A Lewis acid-promoted highly regio- and diastereoselective C(sp3)-C(sp2) cross-coupling reaction between unprotected aryl-substituted 1,2-diols and styryl-, aryl-, heteroaryl-, and polyarylboronic acids has been developed in a one-pot procedure. The regioselective opening of aryl-substituted cyclic boronic esters promoted by a Lewis acid followed by subsequent intramolecular 1,4-transfer of the carbon ligand from boron to a resonance-stabilized benzylic carbenium ion minimizing the allylic 1,3-strain in a stereoselective fashion led to the corresponding α-substituted syn-phenylethyl alcohols. The synthetic utility of the method was illustrated by a short and efficient enantioselective synthesis of cherylline diethyl ether (-)-16.

DDQ-Promoted Mild and Efficient Metal-Free Oxidative α-Cyanation of N-Acyl/Sulfonyl 1,2,3,4-Tetrahydroisoquinolines.

A mild and highly efficient metal-free oxidative α-cyanation of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) has been accomplished at an ambient temperature via DDQ oxidation and subsequent trapping of N-acyl/sulfonyl iminium ions with (n-Bu)3SnCN. Employing readily removable N-acyl/sulfonyl groups as protecting groups rather than N-aryl ones enables a wide range of applications in natural product synthesis. The synthetic utility of the method was illustrated using a short and efficient formal total synthesis of (±)-calycotomine in three steps.