Carreño M Carmen, Somoza Alvaro, Ribagorda María, Urbano Antonio
Departamento de Química Orgánica (C-I), Universidad Autónoma. Cantoblanco, 28049 Madrid, Spain.
Chemistry. 2007;13(3):879-90. doi: 10.1002/chem.200600809.
Convergent enantioselective syntheses of angucyclinone-type natural products rubiginones A(2) (2) and C(2) (1) and their 11-methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1-vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe(3) on (SS)-[(p-tolylsulfinyl)methyl]-p-quinol (9) and the elimination of the beta-hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels-Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C-2 or C-3 of the dienophiles 5 or 6, derived from 5-methoxy-1,4-naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C-1 oxidation.
通过使用两个多米诺过程，从一种常见的对映体纯的1-乙烯基环己烯4出发，实现了对环菌素类天然产物鲁比吉酮A(2)（2）和C(2)（1）及其11-甲氧基区域异构体3a和3b的汇聚式对映选择性合成。该二烯合成中的关键步骤是AlMe(3)对(SS)-[(对甲苯基亚磺酰基)甲基]-对苯二酚（9）的立体选择性共轭加成，以及在氧化为砜后消除β-羟基亚砜片段以恢复羰基。第一个多米诺序列包括与亚磺酰基萘醌的狄尔斯-阿尔德反应，随后是亚砜消除。在使用源自5-甲氧基-1,4-萘醌的亲双烯体5或6的C-2或C-3处的亚砜构建四环骨架的汇聚过程中，在环加成步骤中实现了有效的相反区域选择性。由氧气和阳光引发的第二个多米诺过程，使得初始四环加合物在B环芳构化、硅基脱保护和C-1氧化后转化为最终产物。
