Asymmetric Total Synthesis of Shizukaol J, Trichloranoid C and Trishizukaol A

Abstract

The asymmetric total synthesis of three lindenane sesquiterpenoid oligomers, shizukaol J, trichloranoid C and trishizukaol A, has been accomplished concisely in 15, 16 and 18 longest linear steps, respectively. The expeditious construction of molecular architectures was facilitated by Nelson's catalytic asymmetric ketene-aldehyde cycloaddition, a sequence of allylic alkylation/reduction/acidic cyclization to forge a lactone, and a double aldol condensation cascade to construct the 5/6 bicyclic system. Diastereoselective nucleophilic substitution promoted by a phase transfer catalyst constructed the C 11 quaternary stereogenic center, thus prompting synthetic efficacy toward shizukaol J. The synthesis of trichloranoid C and trishizukaol A was achieved after a cascade involving furanyl diene formation and a Diels-Alder reaction, as well as a one-pot sequence involving furan oxidation and global deprotection. Furthermore, our biological evaluation revealed that two compounds exhibited unexpected toxicity against tumor cell lines.

Novel perspective for protein–drug interaction analysis: atomic force microscope

“…The average height (μ) and average roughness (S a ) were used to quantify morphological changes in SA following interaction with aminoglycosides. 32 The result indicated that the height and roughness of SA in drug solutions decreased compared with free SA (Fig. 2B).…”

“…Among the key strengths of our research group is the ability to evaluate the effects of drugs on the interaction of PPI by AFM, which proved to be a feasible approach for enhancing our understanding of PPI processes in the presence of drugs. 32,88,89 Our pioneering work demonstrated that drugs affect PPI via multiple forces. Similar studies on the PPI of myoglobin/antibody emerged, providing information on changes in the binding force and probability, 90 indicating the conformational change of myoglobin after drug treatment.…”