tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-6,7-diacetoxy-1-(4-acetoxy-5-methyl-6-phenylhexyl)-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate | 164215-53-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-6,7-diacetoxy-1-(4-acetoxy-5-methyl-6-phenylhexyl)-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
• 英文别名: tri-tert-butyl (1S,3S,4S,5R,6R,7R)-6,7-diacetoxy-1-((4R,5R)-4-acetoxy-5-methyl-6-phenylhexyl)-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate；Carreira triacetate；tritert-butyl (1S,3S,4S,5R,6R,7R)-6,7-diacetyloxy-1-[(4R,5R)-4-acetyloxy-5-methyl-6-phenylhexyl]-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
• CAS: 164215-53-6
• 化学式: C₄₀H₅₈O₁₅
• 分子量: 778.892
• InChiKey: WUMOIJXBQXKUBE-GHEKOXKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  55
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  197
• 氢给体数：
  1
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-6,7-diacetoxy-1-(4-acetoxy-5-methyl-6-phenylhexyl)-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 Zaragozic acid C 3,4,5-tris-tert-butyl ester
  参考文献：
  名称：

  Synthesis of (+)-Zaragozic Acid C

  摘要：

  DOI：

  10.1021/ja00102a074
• 作为产物：
  描述：

  2,2-Dimethyl-propionic acid (E)-(1R,8S,9R)-9-benzyloxy-9-((R)-2,2-diethyl-[1,3]dioxolan-4-yl)-8-hydroxy-8-hydroxymethyl-1-((R)-1-methyl-2-phenyl-ethyl)-5-oxo-non-6-enyl ester 在 palladium dihydroxide 、 palladium on activated charcoal 、 Lindlar's catalyst 、 calcium carbonate 2,6-二甲基吡啶 、 盐酸 、 二氯乙酸 、 4-二甲氨基吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 四氧化锇 、 N-甲基吲哚酮 、 2-甲基-2-丁烯 、 草酰氯 、 氢气 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 臭氧 、 silver nitrate 、 二甲基亚砜 、 氢化奎尼定 1,4-(2,3-二氮杂萘)二醚 、 三乙胺 、 三甲胺 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 2.0h， 生成 tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-6,7-diacetoxy-1-(4-acetoxy-5-methyl-6-phenylhexyl)-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
  参考文献：
  名称：

  Synthesis of (+)-Zaragozic Acid C

  摘要：

  DOI：

  10.1021/ja00102a074

文献信息

• Total Synthesis of Zaragozic Acid C: Implementation of Photochemical C(sp³)–H Acylation
  作者：Takahiro Kawamata、Masanori Nagatomo、Masayuki Inoue

  DOI：10.1021/jacs.6b13263

  日期：2017.2.8

  Zaragozic acid C (1) was isolated as a potent squalene synthase inhibitor. The 2,8-dioxabicyclo[3.2.1]octane core of 1 is decorated with the three hydroxycarbonyl (C3,4,5), two hydroxy (C4,7), one acyloxy (C6), and one alkyl (C1) groups. Installation of the contiguous C4- and C5-fully substituted carbons presents a formidable synthetic challenge. Our approach to address this problem used a two-step

  萨拉戈齐酸 C (1) 被分离为一种有效的角鲨烯合酶抑制剂。1 的 2,8-二氧杂双环 [3.2.1] 辛烷核心装饰有三个羟基羰基 (C3,4,5)、两个羟基 (C4,7)、一个酰氧基 (C6) 和一个烷基 (C1) . 安装连续的 C4 和 C5 完全取代的碳是一项艰巨的合成挑战。我们解决这个问题的方法使用了两步光化学 C(sp3)-H 酰化。Persilylated d-葡萄糖酸内酯 4 衍生为 3，在 C5-四取代中心具有 1,2-二酮部分。在紫光 LED 照射下 3 的 Norrish-Yang 环化，然后氧化打开所得的 α-羟基环丁酮区域和立体选择性地将 C4 处的富电子叔 C(sp3)-H 键转化为 C(sp3)-C 键以产生2. 密集功能化
• Total synthesis of zaragozic acid C by an aldol-based strategy
  作者：Seiichi Nakamura、Hiroki Sato、Yuuki Hirata、Nobuhide Watanabe、Shunichi Hashimoto

  DOI：10.1016/j.tet.2005.09.030

  日期：2005.11

  quaternary stereogenic centers by a Sn(OTf)2-promoted aldol coupling reaction between an α-keto ester and a silyl ketene thioacetal derived from l- and d-tartaric acids, respectively, (2) the direct introduction of lithium acetylide as the C1 side chain equivalent onto the fully functionalized aldehyde, and (3) construction of the bicyclic core structure by acid-catalyzed internal ketalization under kinetically

  描述了一种通过收敛策略合成泽拉果酸C的主要特征，其中包括（1）通过Sn（OTf）2促进的α-酮之间的醛醇偶合反应同时生成C4和C5季生立体中心。分别衍生自l-和d-酒石酸的酯和甲硅烷基烯酮硫缩醛，（2）将作为C1侧链等价基团的乙炔锂直接引入到完全官能化的醛中，以及（3）通过动力学控制条件下酸催化的内部缩酮化反应。
• Self-Consistent Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C via Controlled Oligomerization
  作者：David A. Nicewicz、Andrew D. Satterfield、Daniel C. Schmitt、Jeffrey S. Johnson

  DOI：10.1021/ja808347q

  日期：2008.12.24

  Despite the prevalence of repeating subunits in chiral natural products, stereocontrolled oligomerization is a largely unexplored strategy for construction of carbon skeletal frameworks. This report describes the use of silyl glyoxylates as dipolar glycolic acid synthons in a controlled oligomerization reaction for the efficient construction of the squalene synthase inhibitor zaragozic acid C. This

  尽管手性天然产物中重复亚基很普遍，但立体控制的低聚化在很大程度上是一种尚未开发的碳骨架构建策略。本报告描述了在受控低聚反应中使用甲硅烷基乙醛酸作为偶极乙醇酸合成子，以有效构建角鲨烯合酶抑制剂 zaragozic 酸 C。这种新方法允许快速、立体控制地形成具有理想保护基团方案的碳骨架，同时最大限度地减少官能团修复和氧化态操作。
• Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C
  作者：Hiroki Sato、Sei-ichi Nakamura、Nobuhide Watanabe、Shun-ichi Hashimoto

  DOI：10.1055/s-1997-6154

  日期：1997.6

  The total synthesis of zaragozic acid C has been achieved by a convergent strategy, wherein the key feature of the construction of 2,8-dioxabicyclo[3.2.1]octane core structure is a simultaneous creation of the C4 and C5 quaternary carbon centers by Sn(OTf)2-promoted aldol coupling reaction between α-keto ester and silyl ketene thioacetal derived from L- and D-tartaric acids, respectively.

  2,8-dioxabicyclo[3.2.1]octane 核心结构的主要特征是通过 Sn(OTf)2 促进的δ-酮酯与硅酮硫代乙醛的醛醇偶联反应同时生成 C4 和 C5 季碳中心。
• (+)-Zaragozic Acid C: Synthesis and Related Studies
  作者：Erick M. Carreira、J. Du Bois

  DOI：10.1021/ja00136a008

  日期：1995.8

  The asymmetric synthesis of the potent squalene synthase inhibitor (+)-zaragozic acid C is described. The synthesis allows for the preparation of multigram quantities of the dioxabicyclooctane core common to all members of this class of fungal metabolites. Supporting studies include (1) the use of [Cr(OAc)(2) . H2O](2) for the stereoselective reduction of ynones to trans enones, (2) an investigation of the diastereoselective dihydroxylation of gamma-alkoxy-alpha,beta-trans trans enones, and (3) nucleophilic addition of Me(3)SiC equivalent to CLi to a dioxabicyclooctanone, wherein the product diastereoselectivity is observed to vary as a function of cosolvents (tertiary amines) and additives (LiBr). In addition, an acylation protocol is reported which permits the regioselective installation of the C(6) O-acyl side chain.