Synthetic studies on oryzalexin S and structurally related diterpenes

Oryzalexin S是一种强效的水稻植物抗毒素，具有一种在自然界中非常罕见的茎甾型二萜结构。雷公醌G是一种具有抑制白介素-1释放活性的二萜类醌，其ab环结构与雷公醌S相似。在本研究中，我们尝试了oryzalexin S和雷公醌G的全合成。考虑到其旋光性，我们选择了Wieland-Mischer酮作为这两种目标化合物的共同起始原料。该酮依次经过以下处理：选择性保护C-9羰基，还原性乙氧羰基化，烯醇三氟化，还原去除TfO基团，用Collins试剂烯丙基氧化，催化加氢，保护C-2羰基，并在C-4位置进行烯醇化，得到一个共同的中间体。该中间体的C-2羰基选择性去保护，然后用锂在液氨中还原，得到米杂醌S的ab环部分，而酯功能转化为羧酸，然后选择性去保护C-2缩醛和溶解金属还原，得到雷公醌g的ab环部分。采用鲁滨逊环合反应合成了含有oryzalexin S c环结构的中间体。通过双michael反应合成了雷公醌G具有完整c环结构的模型化合物。

Oryzalexin S,a potent rice plant phytoalexin, has a stemarane-type diterpenoid structure which is very rare in nature. Triptoquinone G is a diterpenoid quinone with inhibitory activity against interleukin-1 releases, and has a similar AB-ring structure to oryzalexin S.In this research, we attempted the total syntheses of oryzalexin S and triptoquinone G.We chose the Wieland-Mischer ketone as the common starting material for both of the target compounds, considering its availability in optically active forms. This ketone was successively treated as follows : selective protection the C-9 carbonyl, reductive ethoxycarbonylation, enol triflation, reductive removal of the TfO group, allylic oxidation with the Collins reagent, catalytic hydrogenation, protection of the C-2 carbonyl, and enolate methylation at the C-4 position, to give a common intermediate. Selective deprotection of the C-2 carbonyl of this intermediate was followed by reduction with lithium in liquid ammonia to afford the AB-ring moiety of oryzalexin S,while convesion of the ester function to a carboxylic acid followed by selective deprotection of the C-2 acetal and the dissolving metal reduction gave the AB-ring portion of triptoquinone G.In a model system, the synthesis of an intermediate incorporating the C-ring structure of oryzalexin S was accomplished via the Robinson annelation reaction. A model compound of triptoquinone G possessing the complete C-ring structure was also synthesized via the double-Michael reaction.