Bioactive norsesterterpene 1,2-dioxanes from a Thai sponge, Mycale sp

Abstract

Two new norsesterterpene 1,2-dioxanes, mycaperoxides A (2) and B (3), have been isolated from a Thai sponge of the genus Mycale. Their relative structures were determined by X-ray and spectroscopic methods and their absolute configurations assigned by applying the Kusumi and Kakisawa modification of Mosher's method. Both compounds showed significant cytotoxicity and in vitro antiviral activity.

Peroxy natural products

“…70 Synthetic efforts towards mycaperoxide B, originally isolated from a Mycale sp. from Thailand 71 , have been reported using a biomimetic approach. 72,73 2.2 1,2-Dioxolane Carboxylates: Although the majority of cyclic peroxides contain 1,2-dioxanes, while a growing number possess the more rare 1,2-dioxolane ring system.…”

Towards the Total Synthesis of Mycaperoxide B: Probing Biosynthetic Rationale

“…Given that there are three stereogenic centres at C-2Ј, C-3Ј and C-6Ј, and therefore eight possible diastereoisomers, the observed formation of only four such isomers implies some form of stereoselectivity during the cyclisation reaction. As for the 1 H NMR spectrum, although the chemical shifts of the majority of the carbon signals compared very favourably with both mycaperoxide B (1) and its methyl ester (1a), [1] there Scheme 5. Possible formation of up to four diastereoisomers in the Michael addition reaction when using the 6ЈR diastereoisomer.…”

“…The intramolecular cyclisation of the hydroperoxide onto the conjugated methyl ester in 7 was first studied in model system 8 (Scheme 3), which was prepared by using a methodology similar to that previously reported. [13] It was initially decided to attempt the cyclisation reaction under basic conditions (Table 1, entries [1][2][3][4][5][6][7][8]. The conditions that resulted in the optimum formation of the desired 1,2-dioxolane ring 10 (15 %) along with the undesired epoxide 11 (40 %) involved the use of 0.2 equiv.…”

Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae

“…A Thai Mycale sp. yielded the two cyclic peroxides mycaperoxide A (138) and B (139) [111] and two further mycaperoxides, C (140) and D (141), were isolated from an Australian Mycale sp. in addition to the known compounds enantio-sigmosceptrellin A (132), 134, and 135 [106].…”

“…Bicyclic peroxides that share similar structural characteristics to the mycaperoxides include the sigmosceptrellins (e.g., sigmosceptrellin A 133) isolated from the sponge Diacarnus laevis [108,109] and diacarperoxides (e.g., diacarperoxide F 144) from the sponge Diacarnus megaspinorhabdosa [116]. Mycaperoxides A (138) and B (139) inhibited the growth of bacteria (Bacillus subtilis and S. aureus), showed antiviral activity with IC 50 values in the range of 0.25-1.0 µg/mL (against Vesicular stomatitis virus and Herpes simplex virus type-1), and showed cytotoxicity with IC 50 values ranging from 0.5-1.0 µg/mL (against P388, A549, and HT-29 cell lines) [111]. Mycaperoxide A (138) has also displayed cytotoxicity with an IC 50 value of 0.45 µM (against six tumour cell lines in an MTT assay), which was in contrast to the inactivity (IC 50 value of 10 µM) of euplectellodiol (145), a norterpenoid (discussed in the next section) that is thought to be an oxidative degradation product of mycaperoxide A (138) [114].…”