STTR Phase I: Semisynthetic Manufacturing of Core Natural Triterpenoids from Outer Birch Bark Extract

The broader impact/commercial potential of this Small Business Innovation Technology Transfer Research Phase I project is to facilitate the manufacturing and commercialization of natural and semi-synthetic products namely core lupane triterpenoids (betulin, betulinic acid, lupeol, betulinic aldehyde) as precursors for drug development and other industrial applications. Research shows that these triterpenoids can be useful agents for prevention and treatment of cancer, chronic inflammation, HIV/AIDS, type 2 diabetes, tuberculosis, metabolic disease, as well as next generation antimicrobials, and vaccine adjuvants. Unfortunately, the complex isolation and/or chemical synthesis of these compounds has resulted in low scale yields at costs of more than US$10,000/kg. The fundamental potential of this project lies in the demonstration of the use of certain selective organic reactions to produce these high value compounds straight from the complex composition of the natural extract found in the outer bark of the birch tree, a renewable, natural resource found extensively throughout the northern climates. This approach is novel and if successful, can result in significantly higher yields while eliminating multiple complex synthesis steps, thus providing a large diversity of triterpenoids that were previously not available in commercial quantities. The technical objective in Phase I research project is the development of a principally new way of pure natural and semi-synthetic chemical manufacturing from the triterpenoid extract found in the outer bark of the birch tree. The specific objectives of this project are to develop the methods and processes to 1) provide commercial quantities of outer bark, free from impurities and foreign matter, 2) develop the processes to extract the natural triterpenoids (BBE) from the outer bark and remove unwanted contaminants. 3) Develop the synthesis processes to convert the triterpene extract to the semi-synthetic precursors necessary with the quality and purity to be used for drug development. This research will provide specially designed processes of bark screening, separation and densification to provide a pure material that can be efficiently and economically processed. Extraction methods will be developed to remove traces of tannins, pigments, suberin, and other unwanted materials. Innovative new ways for the straight semisynthetic production of the triterpenoids directly from BBE, will be developed to lead to the creation of a large scale production process for triterpenoids as fine chemicals.