School of Chemistry and Molecular Biosciences, The University of Queensland , Brisbane, QLD 4072, Australia.
1102 Natural Sciences II, Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
J Org Chem. 2017 Dec 15;82(24):13313-13323. doi: 10.1021/acs.joc.7b02421. Epub 2017 Nov 28.
Three new isocyanoditerpenes (5-7) have been characterized from Australian specimens of the nudibranch Phyllidiella pustulosa. The planar structure and (3R,6S,7R) absolute configuration of pustulosaisonitrile-1 were deduced by spectroscopic analyses at 900 MHz informed by molecular modeling, DFT calculations, and computational NMR chemical shift predictions and by comparison of experimental electronic circular dichroism (ECD) data with TDDFT-ECD calculations for the truncated model compound 8. A catalyst-controlled enantio- and diastereoselective total synthesis of the two most likely diastereomeric candidates for the structure of 5 solidified its (3R,6S,7R,10S,11R,14R) absolute configuration. Three individual enantioselective methods provided stereochemical control at key positions, permitting an unambiguous final structural assignment. Isocyanide 5 and synthetic diastereomers 5a and 5c showed activity against Plasmodium falciparum malaria parasites (IC ∼1 μM).
从澳大利亚裸鳃目动物 Phyllidiella pustulosa 的标本中分离到三个新的异氰基二萜（5-7）。通过分子建模、DFT 计算和计算 NMR 化学位移预测，以及与截断模型化合物 8 的 TDDFT-ECD 计算的实验电子圆二色性（ECD）数据进行比较，推导出 pustulosaisonitrile-1 的平面结构和（3R,6S,7R）绝对构型。对结构最有可能的两种非对映异构体候选物 5 的立体选择性全合成采用催化剂控制的对映选择性和非对映选择性，使 5 的（3R,6S,7R,10S,11R,14R）绝对构型得以固化。三种单独的对映选择性方法在关键位置提供了立体化学控制，从而可以进行明确的最终结构分配。异氰化物 5 和合成的非对映异构体 5a 和 5c 对疟原虫（IC∼1 μM）表现出活性。
