Pharmacochemical Investigation of Marine Sponge Products

与陆地生物相比，海洋生物由于其特殊的生存环境而代谢产生各种物质，这些物质往往具有各种前所未有的化学结构并显示出显著的生物活性。为了从海洋生物中寻找有药用价值的新物质，我们调查了主要生活在冲绳珊瑚礁的海绵的化学成分。1991年7月和1992年7月，我们在冲绳县龟山和矢山群岛采集了海绵。对这些海绵的脂溶和水溶部分进行了生物测定指导分离，如卤虾毒性、抗真菌和细胞毒活性。到目前为止，我们已经阐明了以下海绵的化学成分1。从海绵Theonella swinhoei中分离得到两个新的3-酮-4-亚甲基类固醇化合物，命名为茶酮和锥形酮，并确定了它们的绝对立体结构。我们还分离了一种新的二聚体类固醇，命名为二羟乙内酯和两个已知的4-亚甲基类固醇。双烯丙酮是一种二聚体类固醇，通过分子间Diels-Alder环加成反应在区域和立体特异性地合成。通过对L1210和KB细胞的细胞毒性实验，从海绵Hyrtios erecta产生的活性成分中分离出5个七萜类化合物：异戊烯内酯、甘露内酯、二甘露内酯、(E)-新甘露内酯和(Z)-新甘露内酯。马诺内酯是由25个异构体(约1：1)混合而成。我们研究并重新确认了这些化合物的4R绝对构型。从海洋海绵Adobe cia sp.中分离到两种新的抗生素聚乙炔。并根据化学和物理化学证据阐明了它们的绝对立体结构。

Due to their unusual living environment as compared with terrestrial organisms, marine organisms, such as marine sponge and octocoral, metabolite and produce a variety of substances which often have various unprecedented chemical structures and exhibit significant biological activities. In search of new pharmaceutically valuable substances from marine organisms, we have investigated the chemical constituents of marine sponges mostly inhabiting the Okinawan coral reefs.We collected marine sponges at Kerama and Yaeyama Islands, Okinawa prefecture, in July 1991 and 1992. The lipid-soluble and water-soluble portions of these marine sponges were subjected to bioassay-guided separation, such as brine-shrimp toxicity, antifungal and cytotoxic activities. So far, we have elucidated the chemical constituents of following marine sponges.1. Two new 3-keto-4-methylene steroids named theonellasterone and conicasterone were isolated from the marine sponge Theonella swinhoei and elucidated their absolute stereostructures. We also isolated a new dimeric steroid named bistheonellasterone together with two known 4- methylene sterols. Bistheonellasterone is a dimeric steroid biosynthesized regio- and stereospecifically by presumable intermolecular Diels-Alder cycloaddition of theonellasterone.2. The examinations of cytotoxicity against L1210 and KB cells led to the isolation of five sesterterpenes, heteronemin, manoalide, secomanoalide, (E)-neomanoalide, and (Z) -neomanoalide, as active principles produced by the marine sponge Hyrtios erecta. Manoalide was obtained as a (ca. 1:1) mixture of 25-epimers. We have examined to reconfirm the 4R absolute configuration of these manoalide family.3. Two new antibiotic polyacetylenes were isolated from an marine sponge Adocia sp. and their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence.