Czuba Ivona R, Zammit Steven, Rizzacasa Mark A
School of Chemistry, The University of Melbourne, Victoria, 3010, Australia.
Org Biomol Chem. 2003 Jun 21;1(12):2044-56. doi: 10.1039/b302460a.
The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.
描述了(+)-rottnestol(1)以及相关海洋海绵代谢产物(+)-raspailols A(5)和B(6)的不对称合成。这些合成路线中的关键步骤是通过Stille偶联形成C9-C10 sp2-sp2键，并将多烯侧链连接到合适的旋光性四氢吡喃核心上。对于rottnestol(1)，通过锡烷7与(R)-或(S)-8之间的偶联，随后进行酸水解，合成了C12的两个差向异构体，通过将合成材料的手性光学数据与天然产物报道的数据进行比较，确定了远程C12立体中心的绝对构型为R。与此一致的是，(12R)-raspailol A(5)由锡烷7和侧链9合成，该化合物与天然材料的数据在旋光方向和比旋光度绝对值等方面也匹配良好。最后，通过锡烷10与碘化物9的结合得到了raspailol B(6)的相同C12差向异构体，其旋光性也与天然产物报道的相似。因此，所有这三种化合物似乎都具有(12R)构型，而核心四氢吡喃环的构型与最初提出的相同。
