在合成研究中,11(9→7)-abeo-Steroid骨架的意外形成,致使巴特拉科托克辛的形成
Hiroyuki Mutoh1, Yuuki Watanabe1, Daiki Kamakura1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo.
Chemical & pharmaceutical bulletin
|April 3, 2024
概括
研究人员开发了一种新型的合成策略,用于强大的类固醇巴特拉毒素. 这种方法使用韦克斯和皮纳科尔合反应高效地组装了类固醇骨架,从而产生了天然产品matsutakone.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 自然产品的合成自然产品的合成
背景情况:
- 巴特拉霍毒素 (1) 是一种在青,鸟类和甲虫中发现的高度有毒的类固醇,以其强大的心脏和神经毒性作用而闻名.
- 之前已经确定了合成路径到巴特拉毒素 (1).
- 有效组装类固醇ABCD环骨架是合成复杂的天然产品,如巴特拉毒素的一个关键挑战.
研究的目的:
- 探索一种替代性和有效的策略,用于组装巴特拉毒素的6/6/6/5个成员的类固醇骨架 (ABCD环) (1).
- 在类固醇合成中研究分子间韦克斯和分子内皮纳科尔合反应的应用.
- 为了实现自然产品的融合合成matsutakone骨架.
主要方法:
- 利用/促进的分子间韦克斯合来连接AB环和D环碎片.
- 采用了二 (SmI2) 介导的分子内皮纳科尔合器.
- 开发了一个11步的融合合成,从2-基-3-氧cyclopent-2-en-1-one开始.
主要成果:
- 韦克斯合器成功连接了AB环和D环碎片.
- 通过SmI2介导的皮纳科尔合并没有产生预期的C环循环.
- 意想不到的是,SmI2促进了α-基基中间体的1,4添加,形成了一个不寻常的11(9→7) -阿贝奥类固醇骨架.
- 松竹石骨架的融合组装是在11个步骤中实现的.
结论:
- 这项研究证明了Weix和SmI2介导反应在类固醇骨构造中的新应用.
- 意想不到的11(9→7) -abeo-steroid骨架的形成突出显示了类固醇修饰的新反应途径.
- 开发的合成策略提供了一条有效的通道到matsutakone骨架,展示了激素化学在复杂分子合成中的实用性.
相关概念视频
01:55Bone Structure
Within the skeletal system, the structure of a bone, or osseous tissue, can be exemplified in a long bone, like the femur, where there are two types of osseous tissue: cortical and cancellous.
01:40Bone Remodeling
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
01:27Growth of Cartilage and Bone Tissue
Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
01:29Bone Disorders
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:24Bone Formation by Endochondral Ossification
Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...