Project description:The silica gel absorbed amino acid salt catalyzed asymmetric intramolecular Robinson annulation reaction has been developed; up to 97% ee was obtained with this readily recoverable organocatalyst.
Project description:An enantioselective strategy for the synthesis of tetracyclic motif 5, representing the northern fragment of norzoanthamine, is presented. Key to the strategy is the use of two asymmetric Robinson annulation reactions that produce the tricyclic ABC ring system with excellent stereoselectivity. Further functionalization at the periphery of the C ring produces compound 5 containing six contiguous stereocenters of the natural product.
Project description:Controlled isomerization of the double bond of certain Diels-Alder reactions provides substrates that, upon oxidation, give rise to products whose gross structure corresponds to that of a Robinson annulation. In these cases, the stereochemistry of the Robinson annulation product reflects the fact that the initial combination occurred in a Diels-Alder mode. Using these principles, we have synthesized carissone and cosmosoic acid. In the latter case, our total synthesis raised serious questions as to the accuracy of the assigned structure of the natural product.
Project description:Among the several variants of the highly useful and versatile Robinson annulation, a particular variation that involves ketones reacting with nonenolizable enones, while the α-carbons of the ketones act as nucleophiles at both steps of this cascade process, remains largely unexplored. Moreover, such a catalytic enantioselective reaction is exceptionally rare. While pursuing catalysis of this transformation, we developed two fluorogenic assays that, in combination with other analytic techniques, enabled rapid screening of several sets of catalysts. The first set of polymer-bound aminourea bifunctional organocatalysts was screened using a two-step fluorogenic protocol, designed for slower (e.g., heterogeneous) catalysts. Robinson annulation of acetone with 4'-nitrochalcone formed 3-(4-nitrophenyl)-5-phenyl-2-cyclohexenone, which, after a "developing" reductive treatment, was converted into the corresponding amino derivative, serving as a fluorescent reporter. On the other hand, a range of potentially faster homogeneous catalyst-cocatalyst systems were examined using a direct assay, where 4'-dimethylaminochalcone is converted into the corresponding cyclohexanone fluorescent reporter already upon annulation with acetone. In both cases, the combination of the fluorogenic protocols with high-performance liquid chromatography-based enantiomeric excess estimation enabled identification of lead catalysts, which promoted the enantioselective version of this variant of the annulation.
Project description:A procedure has been developed for the construction of 7,5-fused ring systems through ring expansion of silyl enol ethers. This method has been applied to the synthesis of an intermediate en route to the natural product, tricholomalide A.
Project description:An enantioselective synthesis of functionalized aza-flavanone derivatives using the N-heterocyclic carbene-catalyzed intramolecular Stetter reaction of sulphoamido benzaldehydes has been reported. This procedure presents the first original approach for synthesizing chiral functionalized flavonoids at the 3-position, containing an all-carbon quaternary stereogenic center. This advancement significantly enriches the chemical toolbox for the preparation of complex nitrogen-containing compounds and opens up new avenues for further research and development in synthetic organic chemistry.
Project description:An enantioselective synthesis of the core framework of neurotrophic Illicium majucin-type sesquiterpenes is described here. This strategy is based on an organocatalyzed asymmetric Robinson annulation and provides an efficient approach for a diversity-oriented synthesis of Illicium natural products that holds remarkable therapeutic potential for neurodegenerative diseases.
Project description:Enantioselective synthesis of chiral isochromans bearing a terminal alkyne moiety has been accomplished by copper-catalysed enantioselective intramolecular propargylic substitution reactions of propargylic esters with alcoholic nucleophiles. This method represents the first successful example which directly introduced a terminal alkyne group into chiral isochromans.
Project description:Hydroalkoxylation is a powerful and efficient method of forming C-O bonds and cyclic ethers in synthetic chemistry. In studying the biosynthesis of the fungal natural product herqueinone, we identified an enzyme that can perform an intramolecular enantioselective hydroalkoxylation reaction. PhnH catalyzes the addition of a phenol to the terminal olefin of a reverse prenyl group to give a dihydrobenzofuran product. The enzyme accelerates the reaction by 3 × 105-fold compared to the uncatalyzed reaction. PhnH belongs to a superfamily of proteins with a domain of unknown function (DUF3237), of which no member has a previously verified function. The discovery of PhnH demonstrates that enzymes can be used to promote the enantioselective hydroalkoxylation reaction and form cyclic ethers.