Dendrobine

Abstract: Dendrobine, a major component of Dendrobium nobile, increasingly draws attention for its wide applications in health care. Here we explore potential effects of dendrobine against influenza A virus and elucidate the underlying mechanism. Our results indicated that dendrobine possessed antiviral activity against influenza A viruses, including A/FM-1/1/47 (H1N1), A/Puerto Rico/8/34 H274Y (H1N1), and A/Aichi/2/68 (H3N2) with IC50 values of 3.39 ± 0.32, 2.16 ± 0.91, 5.32 ± 1.68 μg/mL, respectively. Mechanism studies revealed that dendrobine inhibited early steps in the viral replication cycle. Notably, dendrobine could bind to the highly conserved region of viral nucleoprotein (NP), subsequently restraining nuclear export of viral NP and its oligomerization. In conclusion, dendrobine shows potential to be developed as a promising agent to treat influenza virus infection. More importantly, the results provide invaluable information for the full application of the Traditional Chinese Medicine named “Shi Hu”.

Abstract: Content determination and microscopic observation proved that dendrobine accumulation in the stem of Dendrobium nobile Lindl. increased after infection with mycorrhizal fungus MF23 (Mycena sp.). Large-scale transcriptome sequencing of symbiotic and asymbiotic D. nobile revealed that 30 unigenes encoding proteins were possibly related to the biosynthesis of dendrobine sesquiterpene backbone. A qRT-PCR experiment of 16 unigenes, selected randomly, proved that there were significant changes in the expression levels of AACT, MVD, PMK and TPS21 at 9 weeks after inoculation. These results implied that MF23 might stimulate dendrobine biosynthesis by regulating the expressions of genes involved in the mevalonate (MVA) pathway. The biogenetic pathway of dendrobine was suggested systematically according to the structural features of dendrobine alkaloids and their sesquiterpene precursors, which implied that post-modification enzymes might play a major role in dendrobine biosynthesis. Thus, genes encoding post-modification enzymes, including cytochrome P450, aminotransferase and methyltransferase, were screened for their possible involvement in dendrobine biosynthesis. This study provides a good example of endophytes promoting the formation of bioactive compounds in their host and paves the way for further investigation of the dendrobine biosynthetic pathway.

Abstract: A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels--Alder cycloaddition reaction (IMDAF) of furanyl carbamates bearing tethered alkenyl groups. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using this methodology. It was possible to carry out a stereoselective reduction of the initially formed hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-furan-2-yl)carbamic acid tert-butyl ester. Kende's advanced intermediate 33 was prepared in seven additional steps by standard transformations, thereby completing a formal synthesis of (+/-)-dendrobine.