Institute for Advanced and Applied Chemical Synthesis , Jinan University , Zhuhai 519070 , China.
Department of Food Science and Engineering , Jinan University , Guangzhou 510632 , China.
J Org Chem. 2019 Mar 15;84(6):3431-3466. doi: 10.1021/acs.joc.9b00018. Epub 2019 Mar 4.
The thermally induced electrocyclic ring-opening of C-symmetric ( meso) 6,6-dibromobicyclo[3.1.0]hexanes such as 10 in the presence of the chiral, nonracemic 1°-amine 28 afforded a ca. 1:1 mixture of the diastereoisomeric and chromatographically separable 1-amino-2-bromo-2-cyclohexenes 37 (42%) and 38 (45%). Each of these was elaborated over 13 steps, including Suzuki-Miyaura cross-coupling, radical cyclization, and Pictet-Spengler reactions, into (-)- or (+)-crinane (1 or ent-1, respectively). Variations on these protocols were applied to the total syntheses of (+)- and (-)-11-hydroxyvattitine [(+)- and (-)-3], (+)- and (-)-bulbispermine [(+)- and (-)-4], (+)- and (-)-haemanthamine [(+)- and (-)-5], (+)- and (-)-pretazettine [(+)- and (-)-6], and (+)- and (-)-tazettine [(+)- and (-)-7] as well as (±)-hamayne [(±)-8] and (±)-apohaemanthamine [(±)-9]. A number of these alkaloids were synthesized for the first time.
在手性、非外消旋 1°-胺 28 的存在下，热诱导的 C 对称（内消旋）6,6-二溴双环[3.1.0]己烷如 10 的电环化开环反应，得到约 1:1 的两种非对映异构体和可分离的 1-氨基-2-溴-2-环己烯 37（42%）和 38（45%）的混合物。这两种化合物都经过 13 步反应进行了详细研究，包括 Suzuki-Miyaura 交叉偶联、自由基环化和 Pictet-Spengler 反应，得到了 (-)-或 (+)-crinane（1 或 ent-1）。对这些方案进行了修改，应用于 (+)-和 (-)-11-羟基瓦他汀 [(+)-和 (-)-3]、(+)-和 (-)-bulbispermine [(+)-和 (-)-4]、(+)-和 (-)-haemanthamine [(+)-和 (-)-5]、(+)-和 (-)-pretazettine [(+)-和 (-)-6]以及 (+)-和 (-)-tazettine [(+)-和 (-)-7]以及 (±)-hamayne [(±)-8]和 (±)-apohaemanthamine [(±)-9]的全合成。其中一些生物碱是首次合成的。
