An Antifungal Cyclodepsipeptide, Cyclolithistide A, from the Sponge Theonella swinhoei

Abstract

A novel antifungal cyclic depsipeptide, cyclolithistide A (1), was isolated from a marine sponge, Theonella swinhoei. The structure of cyclolithistide A, which contains the unique amino acids 4-amino-3, 5-dihydroxyhexanoic acid, formyl-leucine, and chloroisoleucine, was elucidated through a combination of spectroscopic techniques. Thirteen additional specimens of T. swinhoei and three of Theonella conica were examined in this study. Many contained the two cyclic peptides, motuporin (2) and theonellapeptolide 1d (3), as major components, but none of these were a source of 1. The rationale behind this study and some additional aspects of these unusual results are presented.

A Serendipitous Discovery of Isomotuporin-Containing Sponge Populations of Theonella swinhoei

“…no. 94590), though previously discussed, 14 was not evaluated by the methods used herein. There were 14 compounds profiled as shown in Table 1 21 and theopederin J 11 (see Figure S8).…”

“…The first phenotype is defined by a characteristic red-purple ectosome and a cream-colored endosome, and more than 15 such samples have been examined by our group. 14 We found that the major constituents varied among the swinholides, motuporin or theonellapeptolide Id, but not all compounds were present in all collections. The second also possesses a redpurple ectosome but with a yellow to orange interior.…”

“…All sponges were immediately preserved after collection according to our standard procedure 14 and transported back to the laboratory at ambient temperature. Analytical reversed-phase LCMS using a gradient of 10:90 CH 3 CN/H 2 O to 100% CH 3 CN over 35 min was performed on organic solvent partition extracts 14 (coll.…”

“…Another goal was to be able to reliably locate populations that contained motuporin (1) or the swinholides or both because there is continuing speculation that these compounds could be arising from associated cyanobacteria. 16 None of the 17 specimens 14 we previously examined contained the swinholides, yet 1 was present in 14 of them. Thirteen new collections of T. swinhoei were investigated and to our surprise none of them contained 1, but two were a source of a motuporin diastereomer.…”

“…15 We believed that a careful screening study by LCMS of Indo-Pacific-derived T. swinhoei could allow refinement of observations published in 1998. 14 In contrast to the previous study, we sought definition of both major and minor components. Another goal was to be able to reliably locate populations that contained motuporin (1) or the swinholides or both because there is continuing speculation that these compounds could be arising from associated cyanobacteria.…”