Total Synthesis of Ginkgolide C and Formal Syntheses of Ginkgolides A and B.

Ginkgolides are diterpenes isolated from Ginkgo biloba that exhibit strong anti-inflammatory and neuroprotective properties. The highly complex molecular architecture of ginkgolides, combined with their remarkable biological profile, provides a unique platform for the development of new strategies and methods. Herein, we reported the first total synthesis of ginkgolide C and the formal syntheses of ginkgolides A and B. Our synthesis is based on a functional group strategy guided by the compact structure of ginkgolide, where a series of diastereoselective carbon-carbon bond formations and oxidations are carefully orchestrated.

Modular Total Syntheses of Hyperforin, Papuaforins A, B, and C via Gold(I)-Catalyzed Carbocyclization.

The remarkable biological activities of polyprenylated polycyclic acylphloroglucinols (PPAPs) combined with their highly oxygenated and densely functionalized frameworks have stimulated the interest of synthetic organic chemists over the past decade. Herein, we report the concise total syntheses of four natural products PPAPs, of which some have antibacterial properties, notably hyperforin and papuaforin A. The salient features of this strategy are the short and gram-scalable synthesis of densely substituted PPAPs scaffolds via a Au(I)-catalyzed carbocyclization and the late-stage functionalization for a unified access to a wide variety of PPAPs.

Syntheses of Cyclopropyl Analogues of Disorazoles A1 and B1 and Their Thiazole Counterparts.

Modular syntheses of disorazoles A1 and B1 analogues in which the epoxide moieties of the natural products were replaced with cyclopropyl units have been achieved. Targeted as part of a structure-activity relationships study, these syntheses were successfully extended to the thiazole counterparts of these analogues. The retrosynthetically defined fragments were assembled through Yamaguchi esterification, Cu/Pd-catalyzed cross-coupling, Yamaguchi macrolactonization, and Cu-catalyzed cross-coupling as the key reactions. Further synthetic and biological investigations of such analogues are expected to lead to the discovery and development of potential payloads for antibody-drug conjugates as targeted cancer therapies.

Total Syntheses of Disorazoles A1 and B1 and Full Structural Elucidation of Disorazole B1.

Described herein are the first total syntheses of naturally occurring antitumor agents disorazoles A1 and B1 and the full structural assignment of the latter. The syntheses were achieved through convergent strategies employing enantioselective constructions of the required building blocks, including a novel Sharpless epoxidation/enzymatic kinetic resolution of stannane-containing substrates that led selectively to both enantiomeric forms of an epoxy vinyl stannane, and a series of coupling reactions, including a Wittig reaction, a Suzuki coupling, a Stille coupling, a Yamaguchi esterification and a Yamaguchi macrolactonization.

Synthesis and Isolation of Organogold Complexes through a Controlled 1,2-Silyl Migration.

During our efforts toward the synthesis of naturally occurring polyprenylated polycyclic acylphloroglucinol using a Au(I)-catalyzed 6-endo dig carbocyclization, we isolated stable vinyllic gold intermediates. Optimization lead to isolated yields of up to 98%, using 2-(di-tert-butylphosphino)biphenyl as the ligand. This transformation is derived from a silyl rearrangement that can be fully controlled according to the nature of the substituent on the ynone. This selective transformation does not require basic conditions to prevent protodeauration. These vinylgold complexes are the first isolated intermediates during a silyl migration with gold(I). More than 16 new organogold complexes were synthesized and characterized by single-crystal X-ray diffraction. Reactivity of these complexes is also presented.

Total syntheses of hyperforin and papuaforins†A-C, and formal synthesis of nemorosone through a gold(I)-catalyzed carbocyclization.

The remarkable biological activities of polyprenylated polycyclic acylphloroglucinols (PPAPs) combined with their highly decorated bicyclo[3.3.1]nonane-2,4,9-trione frameworks have inspired synthetic organic chemists over the last decade. The concise total syntheses of four natural products PPAPs; hyperforin and papuaforins A-C, and the formal synthesis of nemorosone are reported. Key to the realization of this strategy is the short and scalable synthesis of densely substituted PPAP scaffolds through a gold(I)-catalyzed 6-endo-dig carbocyclization of cyclic enol ethers for late-stage functionalization.

One-pot Diels-Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework.

The rapid synthesis of bicyclo[m.n.1]alkanone cores possessing quaternary carbon centers adjacent to a bridged ketone represents a significant synthetic challenge. This type of architectural feature is embedded in various complex biologically active compounds such as hyperforin and garsubellin A. Herein, we report a highly diastereoselective one-pot Diels-Alder reaction/Au(I)-catalyzed carbocyclization to generate bicyclo[3.3.1]alkanones in yields ranging from 48-93%.

Gold-catalyzed synthesis of carbon-bridged medium-sized rings.

Bicyclo[m.n.1]alkenone frameworks possessing quaternary carbon centers adjacent to a bridged ketone are frequently found in bioactive natural products. Although several methods have been developed to construct such frameworks, most of them are specific to a particular scaffold. Herein, we report a mild and highly efficient method to generate carbon-bridged frameworks of various sizes using phosphino gold(I) catalysts.