Chakraborty Tushar Kanti, Chattopadhyay Amit Kumar
Indian Institute of Chemical Technology,Hyderabad 500007, India.
J Org Chem. 2008 May 2;73(9):3578-81. doi: 10.1021/jo800181n. Epub 2008 Mar 26.
A convergent total synthesis of the cytotoxic natural product cruentaren B is completed in 26 steps (longest linear sequence) with an overall yield of 7.1%. For the construction of the C1-C11 benzolactone fragment of the molecule, the key steps used were O-methylation, using a Mitsunobu reaction, a Stille coupling method to construct the C7-C8 bond, and a Brown's asymmetric crotylboration reaction for the direct enantioselective installation of the two chiral centers present in this fragment. For diastereoselective installation of the chiral centers in the C12-C20 polyketide fragment, an Evans syn aldol reaction on a chiral aldehyde, derived from methyl (R)-3-hydroxyl-2-methylpropionate, and subsequently a Mukaiyama aldol reaction were employed. For the construction of the C21-C28 tail, a "non-Evans" syn aldol reaction was used. The three fragments were coupled by an SN2 reaction and a Wittig olefination reaction followed by standard functional group manipulations to furnish the target molecule.
细胞毒性天然产物cruentaren B的汇聚式全合成以26步（最长线性序列）完成，总产率为7.1%。对于该分子C1-C11苯并内酯片段的构建，关键步骤包括使用 Mitsunobu 反应进行O-甲基化、采用Stille偶联方法构建C7-C8键，以及通过Brown不对称巴豆基硼酸化反应直接对映选择性地引入该片段中存在的两个手性中心。对于C12-C20聚酮片段中手性中心的非对映选择性引入，采用了对源自(R)-3-羟基-2-甲基丙酸甲酯的手性醛进行的Evans顺式羟醛反应，随后进行Mukaiyama羟醛反应。对于C21-C28尾部的构建，使用了“非Evans”顺式羟醛反应。通过SN2反应和Wittig烯烃化反应将这三个片段偶联起来，随后进行标准官能团操作以得到目标分子。
