School of Chemistry , University of Wollongong , Wollongong , New South Wales 2522 , Australia.
Research School of Chemistry , Australian National University , Canberra , ACT 2601 , Australia.
J Nat Prod. 2019 Feb 22;82(2):358-367. doi: 10.1021/acs.jnatprod.8b00879. Epub 2019 Feb 4.
Hyacinthacines C and C are natural products that were isolated from Hyacinthoides non-scripta and Scilla socialis in 1999 and 2007, respectively. Despite their different H NMR and C NMR spectroscopic data, these compounds have been assigned the same structures, including absolute configurations. This work details the total synthesis of natural (+)-hyacinthacine C, whose structure is confirmed as being the C-6 epimer of that reported. The synthetic strategy focused on inverting the configuration at C-1 of the final hyacinthacines via operating the inversion at the corresponding carbon atom in three previously synthesized intermediates. To do this, the advanced intermediates were subjected to Swern oxidation, followed by a stereoselective reduction with L-Selectride. This approach led to the synthesis of (+)-5 -epi-hyacinthacine C (15), the corrected structure for (+)-hyacinthacine C (19), (+)-6,7-di- epi-hyacinthacine C (23), and (+)-7- epi-hyacinthacine C (29). Glycosidase inhibition assays revealed that (+)-hyacinthacine C (19) proved the most active, with IC values of 33.7, 55.5, and 78.2 μM, against the α-glucosidase of rice, human lysosome, and rat intestinal maltase, respectively.
海葱苷 C 和 C 是分别于 1999 年和 2007 年从海葱和西班牙大蒜中分离得到的天然产物。尽管它们的 1H NMR 和 13C NMR 谱数据不同，但这些化合物被赋予了相同的结构，包括绝对构型。本工作详细描述了天然 (+)-海葱苷 C 的全合成，其结构被确认为报道的海葱苷 C 的 C-6 差向异构体。合成策略集中于通过在三个先前合成的中间体中相应碳原子上进行翻转操作，反转最终海葱苷中 C-1 的构型。为此，将高级中间体进行 Swern 氧化，然后用 L-Selectride 进行立体选择性还原。这种方法导致 (+)-5-差向海葱苷 C（15）、(+)-海葱苷 C（19）、(+)-6,7-二差向海葱苷 C（23）和 (+)-7-差向海葱苷 C（29）的合成。糖苷酶抑制试验表明，(+)-海葱苷 C（19）对水稻 α-葡萄糖苷酶、人溶酶体和大鼠肠麦芽糖酶的 IC50 值分别为 33.7、55.5 和 78.2 μM，活性最强。
