Synthetic Studies on Forskolin and Its Related Compounds

Labane diterpene forskolin，从印度草药Coleus forskolii的根源中分离出来，已经展示出具有spasmolytic、cardiotonic和platelet聚集抑制活性的高密度剂，并且还证明了在各种各样的tissue中作为一种独特和潜在的刺激剂。拥有它的治疗潜力，对Glaucoma产生强烈的心脏故障和边缘性哮喘偶联，与一个物质结构挑战， Forskolin具有elicited considerable synthetic attention。有超过100个来自福斯科林及其同源物的模拟，并通过1个alpha-OH、9个alpha-OH和11个碳基的结构活动关系被认为对以上生物活性作出反应。我们已经建立了一个研究指导，以指导Forskolin的总合成及其模拟，以从自然Forskolin中准备好更多的结构信息-A ... More 城市关系和使活动的不同种类的福斯科林展览不同。通过我们在大鼠半胱氨酸膜中的总合成，我们的腺素循环酶的活性（<加-minus>）-forskolin被发现是由于天然forskolin的潜力而产生的，而（<加-minus>）-1，6，7-三氧forskolin完全不起作用，但我们预期。我们的注意力集中在（<加减>）的活动上-6，7-双氧肾上腺素，因为它并没有确定6 beta-OH和7 beta-OH的存在对该活动来说是重要的还是不重要的。结果显示出合成分子完全不活性，因此6-β-OH和/或7-β-OH的存在被提议成为活性的关键。凭借手头上的结果，我们然后将其引向我们的总合成（-）-强力素在自然形式中及其衍生物中的合成及其从同源、不同的三环内酯中间构造的由碱性内聚体Diels-我们现在找到了一个带有四个不对称中心的同源乳酸，它有效地开始了与（S）-propargyl醇可容纳性（S）-BINAL-H减少相应的乙酰酮和成功还原。这条线上的项目会少一些

The labane diterpene forskolin, isolated from the roots of the Indian herb Coleus forskolii, has been shown to be hypotensive agent with spasmolytic, cardiotonic, and platelet aggregation inhibitory activity, and also demonstrated to be a unique and potent stimulator of the enzyme adenylate cyclase in various tissues. Owing to its therapeutic potential for glaucoma, congestive heart failure and bronchial asthma coupled with a substantial structural challenge, forskolin has elicited considerable synthetic attention. There have been synthesized more than 100 analogues from forskolin and its congeners, and through structure-activity relationships of them the region involving 1alpha-OH, 9alpha-OH, and 11-carbonyl has been suggested to be responsible for the above biological activities. We embarked upon an investigation directed towards the total synthesis of forskolin and its analogues otherwise difficult to prepare from natural forskolin with an aim to gain more information of structure-a … More citivity relationships and to differentiate a variety of activities forskolin exhibits. The activitiy of (<plus-minus>)-forskolin obtained by our total synthesis for adenylate cyclase in rat cerebral cortical membranes was half as potent as of natural forskolin, while (<plus-minus>)-1, 6, 7-trideoxyforskolin was totally inactive as we expected. Our attention was focused on the activity of (<plus-minus>)-6, 7-dideoxyforskolin, since it was not determined whether the presence of 6beta-OH and 7beta-OH is important or not for the activity. The result obtained with the synthesized molecule showed total inactivity, and so the presence of 6betaーOH and/or 7betaーOH was proposed to be crucial for the activity. With the above results in hand, we then directed our efforts to the total synthesis of (-)-forskol in natural form and the synthesis of its derivatives from the homochiral,versatile tricyclic lactone intermediate constructed by salient intramolecular DielsーAlder reaction of the butenolide. We have now found that the homochiral lactone with four asymmetric centers was efficiently constructe starting with the (S)-propargyl alcohol obtainable through (S)-BINAL-H reduction of the corresponding acetylenic ketone and successive recrystallization. The project on this line is goi Less