From Wood Industry Side Streams to Drug Candidates: Semisynthesis of Novel Polyphenolic Compounds from Pine Bark Proanthocyanidins
Tammi, Nea (2025-04-15)
From Wood Industry Side Streams to Drug Candidates: Semisynthesis of Novel Polyphenolic Compounds from Pine Bark Proanthocyanidins
(15.04.2025)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
avoin
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2025042329977
https://urn.fi/URN:NBN:fi-fe2025042329977
Tiivistelmä
Proanthocyanidins (PAs) are oligomers or polymers of flavan-3-ols, consisting of one terminal unit and one or more extension units. In B-type PAs, these units are linked via C4–C8 or C4–C6 bonds. A-type PAs, in contrast, feature at least one additional ether bond, such as C2–O–C7 or C2–O–C5. Flavan-3-ols are part of the flavonoid family and are naturally widespread, for example, in pine bark. Natural PAs can be extracted and chromatographically separated from pine bark, then modified into semisynthetic PAs through an acid-catalyzed aldehyde condensation reaction. The semisynthetic PAs feature one or more methylene-bridged (C–CH2–C) linkages between the monomer units. In this thesis, formaldehyde was used as an electrophile in this bridging reaction. With dimers, these semisynthetic interflavan-3-ol linkages demonstrate superior protein precipitation capacities (PPCs) compared to their corresponding natural counterparts according to studies.
Each year, the Finnish forest industry generates three million tons of bark as a byproduct, much of which is currently used for energy production through burning. However, pine bark is a rich source of procyanidins (PCs), a subclass of PAs known, e.g., free-radical scavenging activity and other antioxidant activities. These natural polyphenols can be readily modified with aldehyde condensation reactions, creating novel compounds with potentially enhanced bioactivity.
In this thesis, pine bark PCs were extracted, chromatographically fractionated, and combined based on their retention times and mean degrees of polymerization (mDPs). These chemically different fractions were modified using aldehyde condensation reactions. Additionally, differences among these fractions in the reactions were studied. The formation of methylene-bridged linkages was observed in every DP. The fractions varied from one another in terms of precipitate formation and the number of methylene-bridged linkages formed at each DP. However, higher DP PAs are notoriously challenging to analyze, and this challenge became particularly evident with semisynthetic PAs due to solubility issues of the formed precipitates.
To assess the impact of semisynthetic modifications, the PPCs of methylene-bridged PCs were measured. Key factors influencing PPCs included retention time, mDP of the starting material, and number of methylene-bridged linkages in the product. PCs eluting in the reversed-phase chromatography as a chromatographic hump consisting of mixtures of PC oligomers and polymers caused challenges throughout the thesis, especially at this point since the results presented the combined effects of the PC mixture. While this study provides valuable insights into semisynthetic PCs, further research is needed to fully elucidate their bioactivities and potential in pharmaceutical applications.
Each year, the Finnish forest industry generates three million tons of bark as a byproduct, much of which is currently used for energy production through burning. However, pine bark is a rich source of procyanidins (PCs), a subclass of PAs known, e.g., free-radical scavenging activity and other antioxidant activities. These natural polyphenols can be readily modified with aldehyde condensation reactions, creating novel compounds with potentially enhanced bioactivity.
In this thesis, pine bark PCs were extracted, chromatographically fractionated, and combined based on their retention times and mean degrees of polymerization (mDPs). These chemically different fractions were modified using aldehyde condensation reactions. Additionally, differences among these fractions in the reactions were studied. The formation of methylene-bridged linkages was observed in every DP. The fractions varied from one another in terms of precipitate formation and the number of methylene-bridged linkages formed at each DP. However, higher DP PAs are notoriously challenging to analyze, and this challenge became particularly evident with semisynthetic PAs due to solubility issues of the formed precipitates.
To assess the impact of semisynthetic modifications, the PPCs of methylene-bridged PCs were measured. Key factors influencing PPCs included retention time, mDP of the starting material, and number of methylene-bridged linkages in the product. PCs eluting in the reversed-phase chromatography as a chromatographic hump consisting of mixtures of PC oligomers and polymers caused challenges throughout the thesis, especially at this point since the results presented the combined effects of the PC mixture. While this study provides valuable insights into semisynthetic PCs, further research is needed to fully elucidate their bioactivities and potential in pharmaceutical applications.