2015 年 73 巻 2 号 p. 131-139
Geranyl resorcylates isolated from the fruiting bodies of Hericium erinaceum exhibit a variety of biological activities including stimulation of nerve growth factor (NGF) synthesis, inhibition of collagen-induced platelet aggregation, suppression of endoplasmic reticulum (ER) stress-dependent cell death, plant growth regulation, and so on. This paper describes the divergent total synthesis of the members of geranyl resorcylates with the intention to clarify the structure-activity relationship (SAR) and to supply compounds for further research. The synthesis commenced with preparation of the phthalide core by the newly-developed CuBr2-mediated one-pot multi-functionalization reaction. The C5'-oxidized side chain was synthesized via alkylation with the protected cyanohydrin. Two fragments were assembled by the modified Stille coupling reactions, which were followed by functional group manipulations to furnish the target molecules. From the common intermediates, eleven natural products including hericenones A, B, J and I, hericene A, hericerin, hericenols B-D, and erinacerins A and B were synthesized. Among them, the structures of hericerin and hericenone B were revised as the carbonyl regioisomers of the original assignments. Futhermore, it was suggested that hericenols C and D were artifacts resulting from degradation of hericenol B. This study affords not only the natural product library for SAR study but information to deduce the biosynthetic pathways of geranyl resorcylates.