Gold-catalyzed stereocontrolled oxacyclization/[4+2]-cycloaddition cascade of ketone-allene substrates.

We report the first success on the Au-catalyzed tandem oxacyclization/[4+2]-cycloaddition cascade using ketone-allene substrates to give highly substituted oxacyclics with excellent stereocontrol. In contrast to oxo-alkyne substrates, the resulting cycloadducts are isolable and efficiently produced from a reasonable scope of enol ethers.

Gold-catalyzed stereoselective synthesis of 9-oxabicyclo[3.3.1]nona-4,7-dienes from diverse 1-oxo-4-oxy-5-ynes: a viable formal [4 + 2] cycloaddition on an s-trans-heterodiene framework.

We report a highly stereoselective Au-catalyzed synthesis of 9-oxabicyclo[3.3.1]nona-4,7-dienes from diverse 1-oxo-4-oxy-5-ynes. Formation of these highly strained anti-Bredt oxacycles implies the workability of an unprecedented 1,4-dipole of s-trans-methylene(vinyl)oxonium. This work reveals the feasibility of a formal [4 + 2] cycloaddition on an s-trans-heterodiene framework.

Gold-catalyzed deoxygenative nazarov cyclization of 2,4-dien-1-als for stereoselective synthesis of highly substituted cyclopentenes.

Treatment of 2,4-dien-1-als with allylsilanes and PPh(3)AuSbF(6) (3 mol %) led to formation of 1,4-bis(allyl)cyclopentenyl products; this gold catalyst is superior to commonly used Lewis acids according to catalyst screening. Such gold-catalyzed deoxygenative cyclizations are compatible with various oxygen-, amine-, sulfur-, hydrogen-, and carbon-based nucleophiles. The value of this new catalysis is demonstrated by the diverse annulations of 2,4-dien-1-als with electron-rich alkenes and arenes, providing an easy access to complicated cyclopentenyl frameworks. Structural analysis of annulation products reveals evidence for the participation of Nazarov cyclization. This deoxygenative cyclization is extensible to a tandem intramolecular cyclization/nucleophilic addition cascade, giving polycyclic carbo- or oxacyclic compounds with controlled stereochemistry. This new gold catalysis is applied to a short synthesis of natural compounds of the brazilane family, including brazilane, O-trimethyl-, and O-tetramethyl brazilane.

Biodegradable micelles from a hyaluronan-poly(ε-caprolactone) graft copolymer as nanocarriers for fibroblast growth factor 1.

A novel copolymer (HA-g-PCL) was prepared by grafting hydrophobic poly(ε-caprolactone) (PCL) chains onto the backbone of hydrophilic hyaluronic acid (HA) with a grafting ratio of ∼7%. The copolymer formed micelles with a size of ∼60 nm in aqueous solution over a critical concentration of ∼4 µg mL-1. Each micelle consisted of about four copolymer chains. Fibroblast growth factor 1 (FGF1) may be encapsulated in micelles by various methods. In particular, FGF1 loaded to micelles through 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) conjugation provided efficient (∼87%) and large amount (up to ∼175 µg FGF1 per mg HA-g-PCL, or on average one FGF1 molecule per micelle) of loading as well as reduced burst release of FGF1. FGF1-loaded micelles remained functional after 21 days. Experimental rats receiving FGF1-loaded micelles showed better wound contraction and faster sebaceous gland formation than those receiving free FGF1 or empty micelles. We conclude that novel HA-g-PCL micelles are good nanocarriers for the controlled release of FGF1 and may be applied to encapsulate other bioactive molecules for therapeutic purposes.