Peroxide Natural Products from Plakortis zyggompha and the Sponge Association Plakortis halichondrioides-Xestospongia deweerdtae: Antifungal Activity against Cryptococcus gattii
Peroxide Natural Products from Plakortis zyggompha and the Sponge Association Plakortis halichondrioides-Xestospongia deweerdtae: Antifungal Activity against Cryptococcus gattii
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DOI：
10.1021/acs.jnatprod.5b00951
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发表时间：
2016-03-01
影响因子：
5.1
通讯作者：
Molinski, Tadeusz F.
中科院分区：
文献类型：
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作者：
Jamison, Matthew T.;Dalisay, Doralyn S.;Molinski, Tadeusz F.
加蒂氏隐球菌是一种人类病原体，也是一种致命的播散性真菌疾病的病原体。对巴哈马海绵组织Plakortis halichondrioides-Xestospongia deweerdtae和Plakortis zyggompha的抗真菌提取物进行了研究，发现并分离到6-epi-7，8-二氢plakortie K(1)，plakortie AA(2)和3个新的plakinic酸，N-P(4-6；(5)通过C-13核磁共振化学位移的手势比较和密度泛函计算，确定了化合物4的绝对立体结构。对1-10的立体定向碱促重排皂化反应进行了简单的研究，结果表明新的C-2立体中心的形成受到严格的动力学控制和立体定向构型的影响，C-3为反转中心。在相同的条件下，原激酸M和菌斑9和11对盖氏隐孢子虫有较强的抗真菌活性(MIC90=2.4~36 mU M)，而原激酸N-P则表现出较低的活性。
Cryptococcus gattii is a human pathogen and causative agent of a pernicious, sometimes fatal, disseminated fungal disease. Investigation of antifungal extracts of the marine sponge association Plakortis halichondrioides-Xestospongia deweerdtae and the sponge Plakortis zyggompha from the Bahamas led to the discovery and isolation of 6-epi-7,8-dihydroplakortide K (1), plakortide AA (2), and three new plakinic acids, N-P (4-6; unstable 1,2-dioxolanes bearing benzyl-substituted conjugated dienes), along with known plakinic acids L, K, and M.(5) Chiroptical comparisons and DFT calculations of C-13 NMR chemical shifts were used to assign the absolute stereostructure of 4. The stereospecific base-promoted rearrangement saponification of 1 to 10 was briefly investigated and showed tight kinetic control and stereospecific formation of the new C-2 stereocenter with inversion at C-3. Plakinic acid M and plakortides 9 and 11 exhibited antifungal activity against C. gattii (MIC90 = 2.4 to 36 mu M), but plakinic acids N-P were inactive under the same conditions.