Alotaketals A and B, Sesterterpenoids from the Marine Sponge Hamigera Species that Activate the cAMP Cell Signaling Pathway

Abstract

The new sesterterpenoids alotaketals A (1) and B (2) have been isolated from extracts of the marine sponge Hamigera sp. collected in Papua New Guinea. Their chemical structures were elucidated by analysis of spectroscopic data. Alotaketals A and B have the unprecedented alotane carbon skeleton, and they activate the cAMP cell signaling pathway with EC(50)'s of 18 and 240 nM, respectively.

Marine natural products

“…715 The total syntheses of (À)-alotaketal A (Hamigera sp.) 716 by two independent groups have conrmed the absolute conguration. 717,718 Four sesterterpenoids, phorone A 855, isophorbasone A 856, ansellone B 857 and phorbasone A acetate 858, were isolated from a S. Korean Phorbas sp.…”

A new family of sesterterpenoids isolated around the Pacific Rim

“…6 This landscape has changed signicantly over the past 8 years as an entire new subset of sesterterpenoids has been isolated from marine organisms located around the Pacic Rim swelling their numbers considerably. Eight novel skeletal classes: alotane (1), ansellane (2), secoansellane (3), phorbasane (4), isophorbasane (5), phorane (6), gombane (7) and anvilane (8) have been isolated from marine organisms collected in South Korean, Papua New Guinean and Canadian waters (Fig. 2).…”

“…8). These are the rst and only examples of the bicyclic gombane carbon skeleton (7). 23 Being structurally analogous to the phorbaketals and alotaketals, gombaspiroketals A-C (56-58) share their common spiroketal and hydrobenzopyran moieties, but feature a novel, rearranged cyclohexenyl substituent attached at the C13 quaternary centre.…”

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

“…In contrast, although a pharmacological activity was described, and an IC 50 for inhibition of an enzyme or receptor determined, detailed molecular mechanism of action studies were unavailable at the time of publication for the following 47 marine compounds included in Table 3: alotaketals A and B ( 183 , 184 ) [166]; aquastatin A ( 185 ) [167]; australin E ( 186 ) [168]; lyngbyastatins 9 & 10 ( 187 , 188 ) [169]; brunsvicamides A, B and C ( 189 – 191 ) [170]; carteriosulfonic acids A, B and C ( 192 – 194 ) [171]; Carteriospongia foliascens sesterterpenoids ( 195 , 196 ) [172]; clavatadines D and E ( 197 , 198 ) [173]; fibrosterol sulfates A and B ( 199 , 200 ) [174]; gracilin L ( 201 ) [175]; grassystatins A, B and C ( 141 – 143 ) [133]; 2-hydroxycircumdatin C ( 202 ) [176]; jaspaquinol ( 203 ) [177]; largamides A, B and C ( 204 – 206 ) [178]; largamide D oxazolidine ( 207 ) [179]; Laurencia similis brominated metabolites ( 208 , 209 ) [180]; molassamide ( 210 ) [181]; myrothenone A ( 211 ) [182]; 42-hydroxy-palytoxin ( 212 ) [183]; plectosphaeroic acids A, B and C ( 213 – 215 ) [184]; puupehenone ( 216 ) [177]; Sinularia numerosa oxylipin ( 217 ) [185]; sipholenone E ( 218 ) [186]; spartinoxide ( 219 ) [187]; 23- nor -spiculoic acid B ( 220 ) [188]; tanikolide dimer ( 221 ) [189]; tamulamides A and B ( 222 , 223 ) [190]; terretonins E and F ( 224 , 225 ) [191]; and tetrangulol methyl ether ( 226 ) [192]. …”