During our tenure since 2018, our group has achieved significant milestones in the synthesis of complex and biologically active natural products, highlighted by 54 publications. Key contributions include:
1. Asymmetric Total Synthesis of (+)-Cyclobutastellettolide B: Utilizing the Norrish-Yang photocyclization reaction as a pivotal step, we achieved the synthesis of (+)-cyclobutastellettolide B, a natural product featuring three vicinal all-carbon quaternary stereogenic centers (J. Am. Chem. Soc. 2021, 143, 18287).
2. Semi-synthesis of Abeo-Steroid Bufospirostenin A: Employing a photosantonin rearrangement reaction catalyzed by Co(salen), we achieved regio-selective double-bond isomerization to synthesize bufospirostenin A (J. Am. Chem. Soc. 2022, 144, 2479).
3. Total Synthesis of (+)-Waihoensene: In 2020, we completed a 15-step asymmetric total synthesis of (+)-waihoensene, a challenging molecule with a highly congested tetracyclic core containing four contiguous all-carbon quaternary carbon atoms. Key steps included the Pauson-Khand reaction and hydrogen-atom-transfer for stereoselective installation of the C9 stereogenic center (J. Am. Chem. Soc. 2020, 142, 6511).
4. Application of Pauson-Khand Reaction: We utilized the Pauson-Khand reaction extensively for the total synthesis of complex natural products, including (−)-spirochensilide A (J. Am. Chem. Soc. 2020, 142, 8116).
5. Comprehensive Accounts: Our group published comprehensive review articles in Accounts of Chemical Research, detailing our work in terpenoid synthesis (Acc. Chem. Res. 2019, 52, 480) and the application of the Pauson-Khand reaction in total synthesis of complex natural products (Acc. Chem. Res. 2021, 54, 556).
In addition to our synthesis endeavors, we have expanded our collaborative efforts, notably launching a program in partnership with Shenzhen Bay Lab during the COVID-19 pandemic. This initiative focuses on isolating potential antiviral agents from Anisomeles indica (L.) Kuntze (Labiatae), a traditional Chinese herb known for its historical use in treating inflammation, pain, and influenza.
Also published during this period was a study on the asymmetric total synthesis of (+)-cyclobutastellettolide B (Figure 3b), a natural product which bears three vicinal all-carbon quaternary stereogenic centers, via Norrish-Yang photo-cyclization reaction as a key step (see: J. Am. Chem. Soc. 2021, 143, 18287). We also extended our interested photochemical strategy for the semi-synthesis abeo-steroid bufospirostenin A via a photosantonin rearrangement reaction (J. Am. Chem. Soc. 2022, 144, 2479). In this synthesis, Co(salen) is an effective catalyst, which mediates hydrogen-atom-transfer (HAT) reaction, and achieves regio-selective double-bond isomerization of A to form its complementary product B (Figure 3c).
1) (+)-Waihoensene contains a highly congested and cis-fused tetracyclic core decorated with six contiguous stereogenic centers; among them, four are contiguous all-carbon quaternary carbon atoms, which represents a challenging molecule for organic synthesis. In 2020, we published a 15-step asymmetric total synthesis of the polycyclic natural product (+)-waihoensene by using Pauson-Khand reaction and a hydrogen-atom-transfer to stereoselective installation of its C9 stereogenic centeras as key steps (Figure 3d) (J. Am. Chem. Soc. 2020, 142, 6511). We also employed the Pauson-Khand reaction as a key step for the total synthesis of complex natural products (−)-spirochensilide A (J. Am. Chem. Soc. 2020, 142, 8116). Finally, during this period we also published two comprehensive accounts articles highlighting our groups work in both the terpenoid synthesis (see: Acc. Chem. Res. 2019, 52, 480) and application of Pauson-Khand reaction to in total syntheses of complex natural products (see: Acc. Chem. Res. 2021, 54, 556).
In addition to our total synthesis research, we have accelerated our collaborative program within the laboratories of Shenzhen Bay lab during the time of COVID-19. Notably, we initiated a program to isolate antiviral agents from traditional Chinese herb medicine Anisomeles indica (L.) Kuntze (Labiatae), which has traditionally been used for the treatment of inflammation, pain and influenza.
