Flueggines A and B的全合成研究

Flueggines A and B, a structurally complex alkaloid, is reported to have the potent cytotoxicity against several cancer cell lines. Owing to its complex chemical structure and good anti-cancer activities, Flueggines A and B have attracted world-wide attention of synthetic chemists. While only one total synthese of flueggine A has been published so far, it has suffered from a long reaction sequence and low overall yield. The total synthesis of flueggine B hasn't been published yet. Therefore, it is still in need of more efficient and practically feasible synthetic strategies for the synthesis of flueggines A and B. The further biological studies can be performed based on the success of the synthesis of flueggines A and B. In this proposal, the authors plan to use a novel and divergent strategy to construct the flueggines A and B from three building blocks, which may be synthesized using readily available starting materials, cheap regular reagents, and conventional reaction conditions.

Flueggines A 和 B 是一个具有多环结构的生物碱，同时具有较好的抗肿瘤活性。由于复杂的化学结构和抗肿瘤活性生物活性，吸引了世界上许多合成化学家的关注。目前有一个Flueggine A全合成的报道，但所报道的合成路线较长，总产率低，从而限制了对该分子的成药性研究。Flueggine B的全合成尚未见报道。本项目拟采取全新的合成路线，采用高度汇聚式的合成策略，将Flueggines A和B的复杂结构通过分割简化成三个简单的合成结构砌块。同时，从廉价易得的商业原料开始，使用简单的试剂和常规易操作的反应就可以分别得到各个合成砌块。

Flueggines A 和 B 是一个具有多环结构的生物碱，同时具有较好的抗肿瘤活性。由于复杂的化学结构和抗肿瘤活性生物活性，吸引了世界上许多合成化学家的关注。我们采取全新的合成路线， 采用高度汇聚式的合成策略，完成了 Flueggines A 和 B的全合成。 以此为基础，利用天然产物中的活性片段，我们设计合成了全新的Nampt小分子抑制剂和Class I HDAC选择性抑制剂。该类化合物的初步体内药效学评价及急性毒性评价同样体现了其低毒、高效的特点。项目执行期间，我们培养了3名硕士和5名博士。