Abstract
Ophiorrhiza plants belonging to Rubiaceae are known to produce indole alkaloids including camptothecins with potent antitumor activity as well as β-carboline-type alkaloids. To discover new biologically active natural products, we carried out the chemical investigation of the alkaloids in Ophiorrhiza trichocarpon, resulting in the isolation and structure elucidation of six new indole alkaloid glycosides, OTM1-6 (2-7). By spectroscopic analyses, OTM1 (2) and OTM2 (3) were found to have the basic structure of strictosidine, which is a key and pivotal biogenetic intermediate to camptothecin and monoterpenoid indole alkaloids. Characteristically, both alkaloids have a lactam function in the C-ring and a biose residue in the molecule. They are a pair of diastereomers of 5-keto-6'-glucopyranosyl dolicantoside at a biose linkage. The two glucose units in 2 form a biose linkage, a-glucopyranosyl-(1→6)-β-glucopyranoside which is connected to the C-21 hemiketal oxygen. On the other hand, a biose linkage in 3 is β-glucopyranosyl-(1→6)-β-glucopyranoside. OTM3 (4) is a methanol adduct of 3,4,5,6-tetradehydrodolichantoside (9) at C-16-C-17 double bond. Its relative stereochemistry was deduced from the coupling constants and NOE correlations. OTM4 (5) is a 6'-trans-feruloyl derivative of 9. OTM5 (6) is a 3,4,5,6-tetradehydrodolichantoside-related alkaloid having a carbonyl group at C-5 position in the C-ring. OTM6 (7) is deduced to be a strictosidinic acid-related alkaloid having an unprecedented skeleton with 1,2-dicarbonyl function at C-5 and C-6 position in the C-ring as well as the double bond between C-3 and C-14. This is the first example of monoterpenoid indole alkaloids with this unique skeleton. The absolute configuration of sugar unit in OTM1 (2), OTM3 (4), OTM5 (6), and OTM6 (7) was determined to be D-form by means of a combination of enzymatic hydrolysis and HPLC analysis.
