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

STTR 第一阶段：从外桦树皮提取物中半合成生产核心天然三萜类化合物

• 批准号: 1549685
• 负责人: Brian Garhofer
• 金额: $ 22.5万
• 依托单位: Betula Extractives, LLC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1549685&HistoricalAwards=false
• 关键词: STTR; Phase; Semisynthetic; Manufacturing; Core

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.

这个小企业创新技术转让研究第一阶段项目的更广泛影响/商业潜力是促进天然和半合成产品的生产和商业化，即核心的狼烷三萜（白桦素、白桦酸、狼皮醇、白桦醛）作为药物开发和其他工业应用的前体。研究表明，这些三萜类化合物可用于预防和治疗癌症、慢性炎症、艾滋病毒/艾滋病、2型糖尿病、结核病、代谢性疾病，以及下一代抗菌剂和疫苗佐剂。不幸的是，这些化合物的复杂分离和/或化学合成导致了低规模产量，成本超过10,000美元/公斤。该项目的根本潜力在于演示使用某些选择性有机反应，直接从桦树树皮中发现的天然提取物的复杂成分中生产这些高价值化合物，桦树是一种可再生的自然资源，广泛存在于整个北方气候中。这是一种新颖的方法，如果成功，可以大大提高产量，同时消除多个复杂的合成步骤，从而提供以前无法实现商业数量的多种三萜化合物。第一阶段研究项目的技术目标是开发一种主要的纯天然和半合成化学制造的新方法，从桦树的外层树皮中发现三萜提取物。该项目的具体目标是开发方法和工艺，以1)提供商业数量的无杂质和异物的外树皮，2)开发从外树皮中提取天然三萜（BBE）并去除不需要的污染物的工艺。3)开发合成工艺，将三萜提取物转化为具有用于药物开发的质量和纯度所需的半合成前体。本研究将提供专门设计的树皮筛选、分离和致密化工艺，以提供一种可以高效、经济地加工的纯材料。提取方法将被开发以去除微量的单宁、色素、木质素和其他不需要的物质。将开发从BBE直接半合成生产三萜类化合物的创新新方法，从而建立大规模生产三萜类精细化学品的工艺。