Streamlined construction of a natural product framework
Nature makes biologically active organic molecules bearing complex polycyclic frameworks equipped with functional groups so efficiently from simple starting materials. For example, arylnaphthalide lignan natural products derived from plants, such as diphyllin, justicidin A, taiwanin E, and neojusticidin A, have diverse biological activities, including antiplat, anti-inflammatory, antiviral, and cytotoxic activities.
All these significant molecules has a common structural motif: 9-phenyl-1,3-dihydronaphtho[2,3-c]furan-4-ol. Therefore, the development of an efficient process that enables a short-step assembly of this polycyclic motif from simple acyclic starting materials has been an important subject in organic chemistry.
We envisioned that a transition-metal (TM)-catalyzed carboxylative cyclization and a photopromoted oxidative aromatization can be integrated into a single sequential process to realize the streamlined assembly of arylnathalenes from readily available 1,7-diaryl-1,6-diynes. Actually, various fused 4-phenylnaphthalene-1-yl carboxylates were synthesized in two steps using a ruthenium-catalyzed hydrocarboxylative cyclization of 1,7-diaryl-1,6-diynes with carboxylic acids and subsequent oxidative photocyclization. The key to success of this integral process is the stereoselective formation of exocyclic 1,3-dienyl ester intermediates via the ruthenium-catalyzed reaction.
Based on our previous analysis of the mechanism by DFT calculations, we successfully achieved the optimal reaction conditions using tetrabutylammonium chloride as an additive that suppresses the undesired dissociation of the chloride ligand from the ruthenium catalyst. In addition, we demonstrated that the diversification of the arylnaphthalene product is also possible using late-stage C–H functionalization reactions, such as C–H oxidation and C–H alkenylation. As such, arylnaphthalides and 8,10-dihydrobenzo[de]furo[3,4-h]chromene were obtained. the library of natural-product-like molecules. Thus TM-catalyzed and photopromoted integrated process would open a way to develop a novel natural-product-like molecular library for drug discovery.
Yoshihiko Yamamoto
Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences,
Nagoya University, Chikusa, Nagoya, Japan
Publication
A Combined Transition-Metal-Catalyzed and Photopromoted Process: Synthesis of 2,3-Fused 4-Phenylnaphthalen-1-yl Carboxylates from 1,7-Diaryl-1,6-diynes.
Yamamoto Y, Mori S, Shibuya M.
Chemistry. 2015 Jun
Related Articles:
![]() | Postponed protonation under competitive conditions in… The readily available α,β-unsaturated compound (Michael acceptor) serves as one of the most important building blocks in synthetic chemistry, which is widely used in conjugate addition reaction. The characteristic of… |
![]() | Short hydrogen bonds in proteins and their quantum… The assembly of linear polypeptide chains into functional three-dimensional protein architectures involves a unique force called hydrogen bonding. A typical hydrogen bond forms when the donor and acceptor groups approach… |
![]() | The complementary anti-inflammatory and anticancer activity… Inflammation is an important and extremely complex biological process involving a high number of mediators responsible for the activation of multiple cascades, providing a wide range of possible targets for… |
![]() | Chemoselective Intramolecular carbene C-H insertions of… The transition-metal-catalyzed intramolecularly aliphatic and aromatic C-H insertions of diazo amides provide useful and important transformations to efficiently synthesize nitrogen-containing heterocycles with the new generated C-C bond. The reactivity of… |
![]() | Multicomponent reactions and palladium catalysis Multicomponent reactions (MCR) are reactions in which three or more substrates react together to form a product. These types of reactions are highly recommendable because MCR’s are atom economic, ideal… |
![]() | Imaging metal nanoparticle adsorption on graphene aerogels The functionalization of porous carbon aerogels and sponge-like materials with metal nanoparticles (NPs) has shown significant promise for several applications, including energy storage and harvesting and environmental remediation. Methods for… |
Leave a Reply
You must be logged in to post a comment.