Leucascandrolide A, a new type of macrolide: The first powerfully bioactive metabolite of calcareous sponges (Leucascandra caveolata, a new genus from the coral sea)
Leucascandrolide A, a new type of macrolide: The first powerfully bioactive metabolite of calcareous sponges (Leucascandra caveolata, a new genus from the coral sea)
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DOI：
10.1002/hlca.19960790107
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发表时间：
1996-01-01
影响因子：
1.8
通讯作者：
Pietra, F
中科院分区：
文献类型：
--
作者：
DAmbrosio, M;Guerriero, A;Pietra, F
明白Candrolide A（（+）-1），一种新型的双O-桥连的18元大环内酯，从珊瑚海的一个新属Leucascandra caveolata BOROJEVIC和KLAUTAU的钙质海绵中分离到了一个具有独特侧链的化合物，该化合物显示出很少的CI-分支和广泛的1，3-双氧化作用。（+）-1的酯交换反应得到衍生自侧链的甲酯3和衍生自大环内酯部分的5-羟基衍生物（+）-2，其在C（5）（轴向）处具有天然构型。从（+）-2获得的Mosher ′ s MTPA酯4和5显示分散的Δ Δ =（Δ（S）-Δ（R））数据。然而，通过酮（+）-6，构型a1 C（5）的反转导致较少阻碍的5-赤道羟基衍生物（+）-7，其MTPA酯8和9给出一致的Δ-Δ数据，允许指定（+）-7的绝对构型，从而指定（+）-1。（+）-1的结构新奇及其强大的抗真菌和细胞毒性活性可能会重新引起对钙质海绵的兴趣，以前仅限于几乎没有生物活性的2-氨基咪唑。
Leucascandrolide A ((+)-1), a doubly O-bridged 18-membered macrolide of a new type, i.e., showing little CI-branching vs. extensive 1,3-dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucascandra caveolata BOROJEVIC and KLAUTAU from the Coral Sea. Transesterification of (+)-1 gave the methyl ester 3, derived from the side chain, and the 5-hydroxy derivative (+)-2, derived from the macrolide portion and with the natural configuration at C(5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)-2 showed scattered Delta delta = (delta(S) - delta(R)) data. However, inversion of the configuration al C(5) led, via ketone (+)-6, to the less encumbered 5-equatorial hydroxy derivative (+)-7, whose MTPA esters 8 and 9 gave consistent Delta delta data, allowing the assignment of the absolute configuration of(+)-7, and hence of(+)-1. The structural novelty of(+)-1 and its powerful antifungal and cytotoxic activities are likely to renew interest in calcareous sponges, previously limited to scarcely biologically active 2-aminoimidazoles.