School of Chemistry and Molecular Biosciences (SCMB), The University of Queensland, Brisbane, 4072, Australia.
J Org Chem. 2010 Oct 1;75(19):6489-501. doi: 10.1021/jo101224w.
The Caribbean sponges of the genus Plakortis, P. halichondrioides, and P. simplex have provided a series of biologically active furanolactones-the plakortones A-D (1-4) from the former sponge and B-F (2-6) from the latter. The defining motif of the plakortones is a sterically congested 2,6-dioxabicyclo[3.3.0]octan-3-one moiety, the emblematic furanolactone core. This core is efficiently accessed by a palladium(II) mediated hydroxycyclization-carbonylation-lactonization cascade with an appropriate ene-1,3-diol. Total syntheses of plakortones C (3) and F (6) are now described which settle constitutional and stereochemical features in this group of secondary metabolites. Acquisition of plakortone D (4), the most effective activator of SR-Ca(2+)-pumping ATPase, utilized stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 29. A derived lactone aldehyde was then coupled with an independently generated, sulfone-activated side chain unit, 57. The 11,12-E-double bond, carried through the sequence as a protected, stereodefined diol, was released therefrom by stereospecific syn-elimination via an orthoester derivative. In this way, plakortone D (4) was demonstrated to possess the (3S,4S,6S,10R,11E) configuration. Racemic plakortone E (5) was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 52 was assembled first. Plakortone C (3) resulted from a sequence commencing with (R)-(+)-3-hydroxy-2-methylpropionate, with a derived iodide 76 alkylating the enolate of the butyramide 77 generated from (1S,2S)-(+)-pseudoephedrine. The liberated primary alcohol 79 was converted by standard procedures to key enediol 89 which, with the Pd(II) protocol, afforded the major separable plakortones 90 and 91, with the former being identical with natural plakortone C (3). Very mild hydrogenation of 90 afforded a saturated plakortone, identical with natural plakortone F (6), thus establishing its structure and absolute stereochemistry. Available information on the stereoselective routes to plakortones E (5) and B (2) are also outlined, so that the constitution and absolute stereochemistry of plakortones B-F are now established.
加勒比海的 Plakortis 属海绵，如 P. halichondrioides 和 P. simplex，提供了一系列具有生物活性的呋喃内酯，即前一种海绵的 plakortones A-D（1-4）和后一种海绵的 B-F（2-6）。Plakortones 的定义特征是一个空间拥挤的 2,6-二氧杂双环[3.3.0]辛烷-3-酮部分，是标志性的呋喃内酯核心。通过钯（II）介导的羟基环化-羰基化-内酯化级联反应，可以有效地获得这种核心，该反应使用了适当的烯-1,3-二醇。现在描述了 plakortones C（3）和 F（6）的全合成，解决了这组次生代谢物的结构和立体化学特征。通过立体定向二醇的不对称双羟化获得 plakortone D（4），这是最有效的 SR-Ca（2+）-泵ATPase 激活剂，利用了立体定义的内酯核心。然后，衍生的内酯醛与独立生成的磺酰基激活的侧链单元 57 偶联。11,12-E-双键通过立体特异性顺消除通过邻酯衍生物释放，在该序列中作为保护的、立体定义的二醇携带。通过这种方式，证明 plakortone D（4）具有（3S,4S,6S,10R,11E）构型。使用 Pd（II）诱导的序列也获得了外消旋 plakortone E（5），但在这种情况下，首先组装了所需的完整无环系统 52。Plakortone C（3）是从（R）-（+）-3-羟基-2-甲基丙酸酯开始的序列，衍生的碘化物 76 烷基化由（1S,2S）-（+）-伪麻黄碱生成的丁酰胺 77 的烯醇化物。释放的伯醇 79 通过标准程序转化为关键的烯二醇 89，该烯二醇与 Pd（II）方案一起提供了主要可分离的 plakortones 90 和 91，其中前者与天然 plakortone C（3）相同。90 的非常温和的氢化得到了与天然 plakortone F（6）相同的饱和 plakortone，从而确定了其结构和绝对立体化学。还概述了 plakortones E（5）和 B（2）的立体选择性途径的可用信息，因此现在确定了 plakortones B-F 的结构和绝对立体化学。
