[ORG-25]Intramolecular (4+3) cycloaddition of geminally-tethered epoxy enolsilane towards perhydroazulene frameworks

We have extensively studied the intramolecular (4+3) cycloaddition of epoxy enolsilane with various dienes. This system provided a reliable access to bicyclo[5.4.0]undecanes. However, when it comes to bicyclo[5.3.0]decanes, or perhydroazulenes, the efficiency and diastereoselectivity of the cycloaddition deteriorated considerablely.
Thus, we devised the geminally tethered epoxy enolsilanes, Type B to synthesize perhydroazulene frameworks. In contrast to the reaction of vicinally tethered substrates, the perhydroazulene frameworks can be constructed in good yields and high diastereoselectivity.

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[ORG-24]Studies toward the total synthesis of tubingensin B

The synthesis began with a cheap substrates. The DDA reaction works effectively. The dearomative (4+3) cycloaddition successfully built the skeleton of Tubingensin B in one step. Although this step gave low yield for now, we will try to optimize it. And we will try to complete the synthesis starting from the advanced cycloadduct.

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[ORG-23]Application of the intramolecular (4+3) cycloaddition of furan-tethered epoxy enolsilane to the total synthesis of pseudolaric acid B

Based on the development of the (4+3) cycloaddition of epoxy enolsilanes in our group, we applied the asymmetric (4+3) cycloaddition of optically-enriched furan-tethered epoxy enolsilane 4 to achieve the construction of the trans-fused [5.3.0] bicyclic skeleton, then introduced intramolecular Wacker oxidation in one-pot to give the key intermediate 15. This strategy could be a convergent and efficient route towards the asymmetric total synthesis of pseudolaric acid B.

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[ORG-22]Chemical synthesis of immunoglobulin domain of programmed cell death protein 1

Immune checkpoint protein blockade therapy has made a paradigm-shifting change for the cancer therapies. Notably, the advent of Programmed Cell Death Protein 1 (PD-1) antibodies greatly improves 5-year survival rates of cancer patients. However, the low responding yield prevents the further application of this revolutionary therapy. To tackle this issue, we report the first chemical synthesis of PD-1 immunoglobulin domain by employing Ser/Thr ligation (STL) and native chemical ligation. This well-developed synthetic route enables the synthesis of PD-1 protein bearing specific modification to serve as bio-probe for further investigation of low responding yield mechanism in PD-1 therapy.

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[ORG-20]Studies toward the total synthesis of pseudolaric acid B

Pseudolaric acid A (PAA) and pseudolaric acid B (PAB) are the main active constituents of tujingpi, a traditional Chinese herbal medicine for the treatment of dermatological fungal infections. In the past few years, they have enjoyed a resurgence of interest because of the identification of diverse biological activities, including anti-microbial activity, cytotoxicity towards cancer cell lines, and inhibition of tubulin polymerization.
Our group reported the first total synthesis of PAA. However, the carbene cyclization cycloaddition cascade (CCCC) key step proceeded with a low diastereoselectivity (1.6:1). Our second-generation synthesis aims to improve the synthetic route and the selectivity of the key step.

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