Brummond Kay M, Mao Shuli, Shinde Sunita N, Johnston Paul J, Day Billy W
Center for Chemical Methodologies & Library Development, Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Comb Chem. 2009 May-Jun;11(3):486-94. doi: 10.1021/cc900024p.
Forty-four tetracyclic hydroazulenoisoindoles were synthesized via a tandem cyclopropanation/Cope rearrangement, followed by a Diels-Alder sequence from easily available five-membered cyclic cross-conjugated trienones. These trienones were obtained from two different routes depending upon whether R(1) and R(2) are alkyl or amino acid derived functional groups, via a rhodium(I)-catalyzed cycloisomerization reaction. To increase diversity, four maleimides and two 1,2,4-triazoline-3,5-diones were used as dienophiles in the Diels-Alder step. Several Diels-Alder adducts were further reacted under palladium-catalyzed hydrogenation conditions, leading to a diastereoselective reduction of the trisubstituted double bond. This library has demonstrated rapid access to a variety of structurally complex natural product-like compounds via stereochemical diversity and building block diversity approaches.
通过串联环丙烷化/Cope重排，随后从易于获得的五元环状交叉共轭三烯酮进行狄尔斯-阿尔德反应序列，合成了44种四环氢化薁并异吲哚。这些三烯酮根据R(1)和R(2)是烷基还是氨基酸衍生的官能团，通过铑(I)催化的环异构化反应从两条不同的路线获得。为了增加多样性，在狄尔斯-阿尔德步骤中使用了四种马来酰亚胺和两种1,2,4-三唑啉-3,5-二酮作为亲双烯体。几种狄尔斯-阿尔德加合物在钯催化的氢化条件下进一步反应，导致三取代双键的非对映选择性还原。该文库已证明通过立体化学多样性和构建块多样性方法能够快速获得各种结构复杂的天然产物类化合物。
