Department of Chemistry, National Tsing Hua University, Hsinchu, 30013, Taiwan.
Chemistry. 2010 Jan 4;16(1):282-7. doi: 10.1002/chem.200902275.
An efficient short total synthesis of benzo[c]phenanthridine alkaloids including oxyavicine, oxynitidine, and oxysanguinarine is described. Thus, N-methyl-o-bromobenzaldimines 1 b-d undergo regioselective cyclization with 4-(benzo[d][1,3]dioxol-5-yl)but-3-yn-1-ol (2 b) in the presence of [Ni(cod)(2)] (cod=1,5-cyclooctadiene). In situ oxidation of the resultant isoquinolinium salts gives isoquinolinone derivatives 5 b-d with benzo[d][1,3]dioxol-5-yl substitution at the C(3) atom and a (CH(2))(2)OH group at the C(4) atom. Later, oxidation of the alcohol group in 5 b-d to the aldehyde moiety followed by acid-catalyzed cyclization and dehydration completes the total syntheses to give oxyavicine, oxynitidine, and oxysanguinarine in 67, 65, and 60 % yields, respectively. The synthesis requires four steps from o-bromobenzaldehyde derivatives. Transformations of these alkaloids to the other alkaloids in this family are also discussed herein.
描述了苯并[c]菲啶生物碱包括氧阿维辛、氧去甲烟碱和氧化血根碱的高效短总合成。因此，N-甲基-o-溴代苯亚胺 1b-d 在[Ni(cod)(2)]（cod=1,5-环辛二烯）的存在下与 4-(苯并[d][1,3]二恶烷-5-基)丁-3-炔-1-醇（2b）发生区域选择性环化。所得异喹啉鎓盐的原位氧化得到具有苯并[d][1,3]二恶烷-5-基取代基的异喹啉酮衍生物 5b-d，C(3)原子上的取代基和 C(4)原子上的（CH(2))(2)OH 基团。随后，5b-d 中醇基氧化为醛基，然后进行酸催化环化和脱水，完成总合成，分别以 67%、65%和 60%的收率得到氧阿维辛、氧去甲烟碱和氧化血根碱。该合成从 o-溴代苯甲醛衍生物需要四个步骤。本文还讨论了这些生物碱向该家族中其他生物碱的转化。
