Synthetic studies on oryzalexin S and structurally related diterpenes

水稻抗毒素S是一种有效的水稻植物抗毒素，具有在自然界中非常罕见的甾烷型二萜结构。Triptoquinone G是一种具有抑制白细胞介素-1释放活性的二萜醌，与oryzalexin S具有相似的AB环结构。在本研究中，我们尝试了oryzalexin S和triptoquinone G的全合成。考虑到其光学活性形式的可用性，我们选择了Wieland-Mischer酮作为两种目标化合物的共同起始原料。该酮依次经过C-9位羰基选择性保护、还原乙氧基羰基化、烯醇三氟甲磺酸化、还原脱除TfO基团、用柯林斯试剂烯丙基氧化、催化氢化、C-2位羰基保护和C-4位烯醇化物甲基化反应，得到一个通用中间体。该中间体的C-2羰基的选择性脱保护，然后在液氨中用锂还原，得到oryzalexin S的AB-环部分，而酯官能团取代为羧酸，然后C-2缩醛的选择性脱保护和溶解金属还原，得到萘醌G的AB-环部分。在模型系统中，通过罗宾逊加成反应完成引入了米扎菌素S的C-环结构的中间体的合成。通过双Michael反应合成了具有完整C环结构的萘醌G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.