開催日: 2017/09/20 - 2017/09/22
In 2009, we isolated biselyngbyaside (BLS, 1), an 18-membered macrolide glycoside, from marine cyanobacterium Lyngbya sp. collected in Okinawa. BLS and its aglycone biselyngbyolide B (BLLB, 2) show growth-inhibitory activity against HeLa and HL60 cells. In addition, 1 inhibited RANKL-induced osteoclastgenesis and induced apoptosis of mature osteoclasts at a low concentration. In a recent study, we clarified that 1 and 2 strongly inhibited the ATPase activites of SERCA1a and 2a, and determined the X-ray crystal structure of 1 and 2 with SERCA1a. The synthetic studies of biselyngbyasides were reported by several groups. And we reported the total synthesis of biselyngbyolide A. In this conference, we will report about the first total synthesis of biselyngbyolide B and biselyngbyaside. At first, we achieved the total synthesis of BLLB. We prepared the vinyl iodide 5 from 1,3-propanediol and (R)-stannene 6 from glycidol derivartive. The two segments were connected by esterification reaction using Shiina reagent and the 18-membered ring structure was constructed by intramolecular Stille coupling reaction. Finally, TBS group was removed to give BLLB. To synthesize biselyngbyaside, we tried the direct glycosylation reaction from BLLB. However, even with the use of various conditions for the glycosylation reaction the glycoside bond could not been constructed. So, we introduced the sugar moiety before the connection of vinyl iodide 5 and stannane 6. TBS group of vinyl iodide 5 was removed followed by glycosylation reaction to give glycoside 27. Glycoside 27 was converted to carboxylic acid 30 in 5 steps. Carboxylic acid 30 and stannane 6 were connected using Mitsunobu reaction, though Shiina esterification reaction gave no desired compound. Finally, intramolecular Stille coupling reaction and removal of TES groups afforded BLS.