Synthetic modifications of the natural lignan hydroxymatairesinol towards ligands for asymmetric catalysis

Finland has a long history of utilizing wood as fuel, construction material and for paper production. However, modern reality raises the question of more efficient and advanced utilization of wood‐based natural products. One promising family of compounds are lignans, which are highly abundant in wood knots, especially hydroxymatairesinol (HMR). Having a complex structure and few chirally pure stereocenters, HMR could be used for preparation of valuable fine chemicals. One of the most efficient ways to utilize the complex chiral structure would be as ligands in asymmetric catalysis. Herein the development of asymmetric catalysts based on the structure of HMR is described. In the first part of the thesis, the concept of using hydroxymatairesinol as a starting material for creating asymmetric catalysts as well as molecular modeling to confirm the concept are presented. The second part of this work describes the synthetic modification of hydroxymatairesinol towards chiral diols. A series of chiral diols were prepared and examined as ligands in asymmetric catalytic reactions. Parts 3 and 4 are related to the preparation of phosphorous derivatives. Part 3 is concentrated on H‐phosphonates and phosphates prepared from the chiral diols described in the second part. In part 4, the synthesis of chiral phosphines based on the lignan backbone is described. The applications of the phosphines as ligands in rhodium catalyzed asymmetric hydrogenations are disclosed

Synthesis and Evaluation of Anisomelic acid-like Compounds for the Treatment of HPV-Mediated Carcinomas

The vast majority of cervical and 75% of oropharyngeal carcinomas are triggered by infection with a type of high-risk oncogenic human papillomavirus (HPV). It is well-known that E6 and E7 oncoproteins are critical for viral-induced cancer, and hence, they represent valuable targets for therapeutic intervention in HPV-mediated cancers. Our earlier research on the cembranoid, anisomelic acid (AA) showed that, AA has the potential to induce apoptosis in HPV cells by the depletion of E6 and E7 oncoproteins. The present study describes the structure-activity relationship and the evaluation of synthetic AA like compounds, i.e simplified cembranoid-like structures, as HPV inhibitors against some papilloma cell lines. Both from experimental and computational results, we observed that these compounds induced apoptosis by the same E6/E7-based mechanism as AA, but at earlier time points, thus being far more effective than AA. Further, the data indicated that only part of the structure of AA is required for the molecular action. Based on these results, we identified some novel and potential compounds for specific treatment of HPV-associated carcinomas

Oxidative Transformations of Lignans

Numerous oxidative transformations of lignan structures have been reported in the literature. In this paper we present an overview on the current findings in the field. The focus is put on transformations targeting a specific structure, a specific reaction, or an interconversion of the lignan skeleton. Oxidative transformations related to biosynthesis, antioxidant measurements, and total syntheses are mostly excluded. Non-metal mediated as well as metal mediated oxidations are reported, and mechanisms based on hydrogen abstractions, epoxidations, hydroxylations, and radical reactions are discussed for the transformation and interconversion of lignan structures. Enzymatic oxidations, photooxidation, and electrochemical oxidations are also briefly reported

Photocross-Linkable and Shape-Memory Biomaterial Hydrogel Based on Methacrylated Cellulose Nanofibres

In the context of three-dimensional (3D) cell cultureand tissueengineering, 3D printing is a powerful tool for customizing in vitro3D cell culture models that are critical for understanding the cell-matrixand cell-cell interactions. Cellulose nanofibril (CNF) hydrogelsare emerging in constructing scaffolds able to imitate tissue in amicroenvironment. A direct modification of the methacryloyl (MA) grouponto CNF is an appealing approach to synthesize photocross-linkablebuilding blocks in formulating CNF-based bioinks for light-assisted3D printing; however, it faces the challenge of the low efficiencyof heterogenous surface modification. Here, a multistep approach yieldsCNF methacrylate (CNF-MA) with a decent degree of substitution whilemaintaining a highly dispersible CNF hydrogel, and CNF-MA is furtherformulated and copolymerized with monomeric acrylamide (AA) to forma super transparent hydrogel with tuneable mechanical strength (compressionmodulus, approximately 5-15 kPa). The resulting photocurablehydrogel shows good printability in direct ink writing and good cytocompatibilitywith HeLa and human dermal fibroblast cell lines. Moreover, the hydrogelreswells in water and expands to all directions to restore its originaldimension after being air-dried, with further enhanced mechanicalproperties, for example, Young's modulus of a 1.1MA/10.3 kPa from5.5 kPa.Peer reviewe

Photocross-Linkable and Shape-Memory Biomaterial Hydrogel Based on Methacrylated Cellulose Nanofibres

In the context of three-dimensional (3D) cell culture and tissue engineering, 3D printing is a powerful tool for customizing in vitro 3D cell culture models that are critical for understanding the cell-matrix and cell-cell interactions. Cellulose nanofibril (CNF) hydrogels are emerging in constructing scaffolds able to imitate tissue in a microenvironment. A direct modification of the methacryloyl (MA) group onto CNF is an appealing approach to synthesize photocross-linkable building blocks in formulating CNF-based bioinks for light-assisted 3D printing; however, it faces the challenge of the low efficiency of heterogenous surface modification. Here, a multistep approach yields CNF methacrylate (CNF-MA) with a decent degree of substitution while maintaining a highly dispersible CNF hydrogel, and CNF-MA is further formulated and copolymerized with monomeric acrylamide (AA) to form a super transparent hydrogel with tuneable mechanical strength (compression modulus, approximately 5-15 kPa). The resulting photocurable hydrogel shows good printability in direct ink writing and good cytocompatibility with HeLa and human dermal fibroblast cell lines. Moreover, the hydrogel reswells in water and expands to all directions to restore its original dimension after being air-dried, with further enhanced mechanical properties, for example, Young’s modulus of a 1.1% CNF-MA/1% PAA hydrogel after reswelling in water increases to 10.3 kPa from 5.5 kPa.</p