Cephalodiones A–D (1–4), the first example of C19‐norditerpenoid dimers, were isolated and fully characterized from a Cephalotaxus plant. These new skeletal natural products shared a unique tricyclo[6.4.1.12,7]tetradeca‐3,5,9,11‐tetraene‐13,14‐dione core that was capped in both ends with rigid multicyclic ring systems either C2‐symmetrically or asymmetrically. Compounds 1–4 were proposed to be biosynthetically produced by the [6+6]‐cycloaddition of two identical C19‐norditerpenoid troponoids, which was validated by the semisyntheses of dimers 2–4. Moreover, some compounds showed significant inhibition on Th17 cell differentiation.

Primary bile acids (BAs), products of cholesterol metabolism and clearance, are synthesized in the liver and released into the intestine to facilitate the digestion and absorption of lipids. BAs are further converted by gut commensal bacteria into secondary colonic BAs and the metabolism disorder is closely linked to cholestatic liver diseases via regulating immune response. However, the effect and underlying mechanism of these host‐microorganism biliary metabolites on T lymphocyte remain unclear. In the current study, we synthesized a sulfated product of lithocholic acid (LCA), lithocholic acid 3‐sulfate (LCA‐3‐S), and investigated the binding affinity of the BAs metabolites on RORγt, the transcription factor of IL‐17A. Our results demonstrated that the sulfate of LCA, LCA‐3‐S, exhibited better effect than its oxidated metabolite, 3‐oxo‐LCA, binding to RORγt. The results further demonstrated that LCA‐3‐S selectively suppressed Th17 cell differentiation without influence on Th1, Th2, and Treg cells. Collectively, we synthesized the sulfated biliary metabolite LCA‐3‐S and demonstrated that LCA‐3‐S selectively inhibited Th17 cell differentiation by targeting RORγt, indicating that metabolite disorder of BAs resulting in the decrease of LCA‐3‐S probably contributes to the pathogenesis of cholestatic liver diseases.

A Stereospecific Geminal Alkylation Scheme en Route to 114.-Both ketones (I), prepared by a route reported for ketone (Ib) in the preceding article, react with sulfonium salt (II) in a highly stereoselective fashion to provide, after acidic treatment, spiro compounds (III). Under conditions of bis-sulfenylative fragmentation of the cyclobutanone ring, lactones (V) are obtained. An entry to the maleic anhydride moiety of title compounds (depicted in the preceding paper) is the photooxidation of acetate (VI) followed by oxidation with PCC. -(KWON, O.; SU, D.-S.; MENG, D.; DENG, W.; D' AMICO, D. C.; DANISHEFSKY, S.

Cephalodiones A–D (1–4), the first example of C19‐norditerpenoid dimers, were isolated and fully characterized from a Cephalotaxus plant. These new skeletal natural products shared a unique tricyclo[6.4.1.12,7]tetradeca‐3,5,9,11‐tetraene‐13,14‐dione core that was capped in both ends with rigid multicyclic ring systems either C2‐symmetrically or asymmetrically. Compounds 1–4 were proposed to be biosynthetically produced by the [6+6]‐cycloaddition of two identical C19‐norditerpenoid troponoids, which was validated by the semisyntheses of dimers 2–4. Moreover, some compounds showed significant inhibition on Th17 cell differentiation.

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