Total Syntheses of the 3H-Pyrrolo[2,3-c]quinolone-Containing Alkaloids Marinoquinolines A-F, K, and Aplidiopsamine A Using a Palladium-Catalyzed Ullmann Cross-Coupling/Reductive Cyclization Pathway.

Compounds 1-6 and 11 representing key members of the marinoquinoline family of natural products, together with the related marine alkaloid aplidiopsamine A (12), have been synthesized using various combinations of palladium-catalyzed Ullmann cross-coupling and reductive cyclization processes involving a C3-arylated pyrrole as the common intermediate. These natural products have been characterized by single-crystal X-ray analyses and evaluated as inhibitors of acetylcholinesterase (AChE) with congener 2 proving to be the most active.

Total Synthesis of (+)-Viridianol, a Marine-Derived Sesquiterpene Embodying the Decahydrocyclobuta[ d]indene Framework.

A total synthesis of the title sesquiterpene 4 is described that starts with the chiral, non-racemic cis-1,2-dihydrocatechol 10 obtained through the whole-cell biotransformation of p-iodotoluene. Compound 10 is elaborated over seven steps, including Negishi cross-coupling and intramolecular Diels-Alder (IMDA) cycloaddition reactions, to ketone 7 that engages in a photochemically promoted 1,3-acyl migration and so affording cyclobutanone 6. Compound 6 was converted over further steps into the title compound 4.

Alkyl Ethers as Traceless Hydride Donors in Brønsted Acid Catalyzed Intramolecular Hydrogen Atom Transfer.

A new protocol for the deoxygenation of alcohols and the hydrogenation of alkenes under Brønsted acid catalysis has been developed. The method is based on the use of either a benzyl or isopropyl ether as a traceless hydrogen-atom donor, and involves an intramolecular hydride transfer as a key step, which is achieved in a regio- and stereoselective manner.

Studies on the Photochemical Rearrangements of Enantiomerically Pure, Polysubstituted, and Variously Annulated Bicyclo[2.2.2]octenones.

A series of enantiomerically pure bicyclo[2.2.2]octenones, including the lactone-annulated system 26, has been prepared by engaging derivatives of an enzymatically derived and homochiral cis-1,2-dihydrocatechol in inter- or intra-molecular Diels-Alder reactions. Systems such as 26 readily participate in photochemically promoted oxa-di-π-methane rearrangement or 1,3-acyl migration processes to give products such as diquinane 34 or mixtures of cyclobutanone 36 and cyclopropane 38, respectively.

Total Syntheses of the Resorcylic Acid Lactones Paecilomycin F and Cochliomycin C Using an Intramolecular Loh-Type α-Allylation Reaction for Macrolide Formation.

Subjection of the resorcylic ester 16 to a Nozaki-Hiyama-Kishi reaction afforded the 12-membered lactone 17, while treatment of it under the Loh-type α-allylation conditions using indium metal gave the isomeric, 14-membered macrolide 18. Compound 18 was readily elaborated to the resorcylic acid lactone type natural products paecilomycin F and cochliomycin C.

Chemoenzymatic Total Syntheses of the Enantiomers of the Protoilludanes 8-Deoxydihydrotsugicoline and Radudiol.

Chemoenzymatic and stereoselective total syntheses of the non-natural enantiomeric forms of the recently isolated protoilludane natural products 8-deoxydihydrotsugicoline (1) and radudiol (2) (viz. ent-1 and ent-2, respectively) are reported. The key steps involve the Diels-Alder cycloaddition of cyclopent-2-en-1-one to the acetonide derived from enantiomerically pure and enzymatically derived cis-1,2-dihydrocatechol 3, elaboration of the resulting adduct to the tricyclic ketone 12, and a photochemically promoted rearrangement of this last compound to the octahydro-1H-cyclobuta[e]indenone 13.

Modular total syntheses of the marine-derived resorcylic Acid lactones cochliomycins a and B using a late-stage nozaki-hiyama-kishi macrocyclization reaction.

The natural products cochliomycin A (1) and cochliomycin B (2), two resorcylic acid lactones obtained from marine sources, have been prepared in a concise and stereocontrolled manner from the readily accessible building blocks 4-6. Olefin cross-metathesis, trans-esterification and Nozaki-Hiyama-Kishi (NHK) macrocyclization reactions were employed in the key steps. Hydrolysis of the immediate precursor to cochliomycin B affords the resorcylic acid lactone zeaenol (24).

Gold and Brønsted acid catalyzed hydride shift onto allenes: divergence in product selectivity.

A series of allenyl ethers can be transformed into various fused or spiro tetrahydrofurans and tetrahydropyrans following a hydride shift/cyclization sequence. A divergence in product selectivity, which depends on the nature of the catalyst used (Au(I) complex or Brønsted acid), was observed.

Gold(I)-catalyzed rearrangement of propargyl benzyl ethers: a practical method for the generation and in situ transformation of substituted allenes.

A series of benzyl propargyl ethers react with a gold(I) catalyst to furnish variously substituted allenes via a 1,5-hydride shift/fragmentation sequence. This transformation is rapid and practical. It can be performed under very mild conditions (room temperature or 60 degrees C) using terminal as well as substituted alkyne substrates bearing a primary, secondary, or tertiary benzyl ether group. The allenes thus formed can be reacted in situ with an internal or external nucleophile, corresponding to an overall reductive substitution process, to produce more functionalized compounds.