The Structures of Aplysinamisines I, II, and III: New Bromotyrosine-Derived Alkaloids from the Caribbean Sponge Aplysina cauliformis

Abstract

Three new bromotyrosine-derived alkaloids, aplysinamisines I [4], II [5], and III [6], were isolated from the sponge Aplysina cauliformis collected in Puerto Rico and their chemical structures elucidated on the basis of spectroscopic methods. Compounds 4-6 showed marginal antimicrobial activity, and aplysinamisines II [5] and III [6] displayed modest cytotoxicity.

Bromoisoxazoline Alkaloids from the Caribbean Sponge Aplysina insularis

“…1) is a novel bromoisoxazoline deriva tive. The n-BuOH soluble fraction of the crude m ethanolic extract of A. insularis gave seven dif ferent bromotyrosine derivatives namely the pre viously described aerophobin-1 (3) (40.3 mg) (Cimino et al, 1983), aerophobin-2 (2) (21.7 mg) (Cimino et al, 1983), aplysinamisin-1 (5) (3.4 mg) (Rodriguez and Pina, 1993), aplysinamisin-2 (6) (9.7 mg) (Rodriguez and Pina, 1993), purealidin L (4) (29.3 mg) (Kobayashi et al, 1995), 2-(3,5-di-brom-4-methoxyphenyl)ethyltrimethylammonium chloride (13) (33.7 mg) (Ciminiello et a l, 1994) and the novel derivative 14-oxo-aerophobin-2 (1) (11.3 mg), while the EtoAc fraction yielded seven more constituents. Except for the quite unusual marine natural product p-hydroxybenzoic acid ethyl ester (ethylparaben) (14) (4.2 mg) the re maining six compounds belong to the group of bromoisoxazoline alkaloids, namely the known de rivatives aerothionin (7) (91.8 mg) (Fattorusso et a l, 1970), 11-oxo-aerothionin (9) (8.0 mg) (Acosta and Rodriguez, 1992), 11-hydroxy-aerothionin (8) (7.4 mg) (Kernan et a l, 1990), fistularin-3 (10) (72.4 mg) (Gopichand and Schmitz, 1979), 11,19-dideoxyfistularin-3 (11) (3.2 mg) (Kernan et a l, 1990) and methyl (6R, 55')-7,9-dibrom-6-hydroxy-8-methoxy-l-oxa-2-azaspiro[4.5]deca-2,7,9-trien-3-carboxylate (12) (3.2 mg) (Ciminiello et a l, 1994).…”

Construction of novel spiroisoxazolines via intramolecular cyclization/methylation

“…The spiroisoxazolines 11-deoxyfistularin-31 and purealidin Q2 have been shown to be cytotoxic against cancer. Furthermore, other spiroisoxazolines such as aerothionin,3 aplysinamisines I-III,4 and agelorin5 display antifungal, antibiotic, or antimycobacterial activity (Figure 1). Since these and other spiroisoxazoline containing natural products express such a wide array of bioactivities, the synthesis and derivatization of this family of compounds continue to be of interest 6…”

Two Unprecedented Dibromotyrosine-Derived Alkaloids from the Brazilian Endemic Marine Sponge Aplysina caissara

“…Several attempts to transform the guanidine group of 1 into its 2-amino-3,5-dimethylpyrimidine derivative were made, but we only obtained complex mixtures, probably due to the formation of degradation products as previously observed for aplysinamisine II (7). 21 It was not possible to obtain the value of specific rotation or the circular dichroism spectrum of 1 because the sample was lost after the NMR experiments. Nevertheless, we have been able to establish the relative stereochemistry of the bicyclic moiety of caissarine A by comparison of the 1 H and 13 C chemical shifts of H-1, H-5, and CH 2 -7 with the literature data of related compounds.…”