(+)- and (-)-Tedanine, a pair of new enantiomeric indolone alkaloids from the marine sponge Tedania sp.

Abstract (+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2–10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.


Introduction
The marine sponges of genus Tenadia belong to the family Tedaniidae, order Poecilosclerida.At present, two subgenera and six species of Tenadia have been reported, which are widely distributed in the southeast coast of Fujian Province [1] and the coastal areas of Qingdao City, China [2].In addition, it is also distributed in Chiloe Island in Chile [3] and Karama Island in Okinawa, Japan [4].In recent years, a variety of secondary metabolites had been isolated from this genus, mainly including alkaloids [5], sterols [6], peptides [7], macrolides [8], terpenes [9], and lipids [10].These compounds exhibited extensive biological activities, such as cytotoxic [11], antifungal [12], antiviral [13], and anti-inflammatory activities [14], which had attracted extensive attention of the researchers.
The analysis of  21.3 and 10.0].The above data were similar to those of 3-(2-hydroxypropyl)-indole [16], which indicated that 1 could be an indolone alkaloid.With the aid of 1D and 2D NMR experiments, the 1 H and 13 C NMR signals of 1 were assigned as shown in Table 1.
Two spin coupling systems were observed in the 1 H-1 H COSY spectrum.In the HMBC spectrum, the HMBC correlations between NH and C-3/C-3a/C-7, between H-4 and C-3/C-7a, between H-5/H-7 and C-3a as well as between H-6 and C-7a suggested the existence of basic structure of indolone.Moreover, the correlations from H-8 to C-2/C-3a verified the fragment of 2-hydroxybutane was connected to the parent nucleus through C-3-C-8.Additionally, the correlations from 3-OH to C-2/C-3a suggested the remaining hydroxyl group should be attached at C-3.Consequently, the planar structure of 1 was deduced (Figure 2).
However, the relative configuration of 1 could not be determined by NOESY spectrum as there were three chiral centers located on the flexible side chain.In order to determine the relative configuration of 1, DP4þ probability was carried out with four possible configurations of 1a, 1b, 1c, and 1d (Figure S1).The result exhibited that the calculated 13 C NMR data of 1b showed a good agreement with the measured one.In addition, the plausible candidate 1b was determined to have 3 R Ã , 8 R Ã , 9S Ã configurations with 96.66% probability (Table S1).Therefore, the relative configuration of 1 could be described as 1b.

Material
The sponge Tedania sp. was collected from Zhanjiang, Guangdong Province, China, in 2015, which were authenticated by Prof. Shi-Hai Xu (Jinan University).A voucher specimen (No. 2015-S3A) was deposited in the Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou, China.

Extraction and isolation
The sponge Tedania sp.(wet 30.0 kg) was percolated with 95% ethanol to afford the crude extraction (615.0 g), which was suspended in H 2 O and partitioned with petroleum ether, ethyl acetate, and n-butanol, respectively.The ethyl acetate extraction (200.0 g) was applied to silica gel column chromatography with a gradient elution using CHCl 3 /CH 3 OH (100:0 $ 0:100) to yield 7 fractions (Frs.

Disclosure statement
No potential conflict of interest was reported by the authors.