tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-1-(4-acetoxy-5-methyl-6-phenylhexyl)-7-(tert-butoxycarbonyl)oxy-4,6-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate | 171190-04-8

• 英文名称: tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-1-(4-acetoxy-5-methyl-6-phenylhexyl)-7-(tert-butoxycarbonyl)oxy-4,6-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
• 英文别名: tritert-butyl (1S,3S,4S,5R,6R,7R)-1-[(4R,5R)-4-acetyloxy-5-methyl-6-phenylhexyl]-4,6-dihydroxy-7-[(2-methylpropan-2-yl)oxycarbonyloxy]-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
• CAS: 171190-04-8
• 化学式: C₄₁H₆₂O₁₅
• 分子量: 794.934
• InChiKey: BMXCYPSPBZGXQL-FWSPXBTESA-N

物化性质

• 沸点：
  792.6±60.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  56
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  200
• 氢给体数：
  2
• 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]-1-(4-acetoxy-5-methyl-6-phenylhexyl)-7-(tert-butoxycarbonyl)oxy-4,6-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (+)-zaragozic acid
  参考文献：
  名称：

  （+）-杜鹃花酸C的全合成

  摘要：

  描述了（+）-杜鹃花酸C的全合成。关键步骤是酸介导的脱保护丙酮二噻烷去除-缩酮化过程中，有选择地提供的2,8-二氧杂双环[3.2.1]天然产物的辛烷核心，和同时引入C3的，C4和C5的羧酸通过三重氧化。

  DOI：

  10.1016/s0040-4039(98)00485-7
• 作为产物：
  描述：

  tert-butyl (1S,3S,4S,5R,6R,7R)-6,7-diacetyloxy-1-[(4R,5R)-4-acetyloxy-5-methyl-6-phenylhexyl]-4-ethenyl-4-hydroxy-5-(hydroxymethyl)-2,8-dioxabicyclo[3.2.1]octane-3-carboxylate 在 吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 potassium carbonate 、 戴斯-马丁氧化剂 、 4-吡咯烷基吡啶 、 臭氧 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 32.08h， 生成 tri(tert-butyl) [1S,1(4R,5R),3S,4S,5R,6R,7R]-1-(4-acetoxy-5-methyl-6-phenylhexyl)-7-(tert-butoxycarbonyl)oxy-4,6-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
  参考文献：
  名称：

  (+)-Zaragozic Acid C: Synthesis and Related Studies

  摘要：

  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.

  DOI：

  10.1021/ja00136a008

文献信息

• Total Synthesis of (+)-Zaragozic Acid C
  作者：Alan Armstrong、Paul A. Barsanti、Lyn H. Jones、Ghafoor Ahmed

  DOI：10.1021/jo000700m

  日期：2000.10.1

  of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous

  描述了（+）-泽拉果酸C的全合成。合成的关键特征是使用二烯6的双重Sharpless不对称二羟基化反应来控制从C3到C6的四个连续的立体中心的立体化学。通过衍生自二噻吩二亚砜27的阴离子与核心醛12之间的反应引入C 1侧链；一种高产的，酸介导的同时进行的丙酮化物脱保护-二硫乙烷去除-缩酮化方法，仅产生2，8-二氧杂双环[3.2.1]辛烷核心34; 以及新颖的三氧化过程，可以安装三羧酸。
• Total Syntheses of Zaragozic Acids A and C by a Carbonyl Ylide Cycloaddition Strategy
  作者：Yuuki Hirata、Seiichi Nakamura、Nobuhide Watanabe、Osamu Kataoka、Takahiro Kurosaki、Masahiro Anada、Shinji Kitagaki、Motoo Shiro、Shunichi Hashimoto

  DOI：10.1002/chem.200601212

  日期：2006.12.4

  A carbonyl ylide cycloaddition approach to the squalene synthase inhibitors zaragozic acids A and C is described. The carbonyl ylide precursor 8 was synthesized starting from di-tert-butyl D-tartrate (47) via an eleven-step sequence involving the regioselective reduction of the mono-MPM (MPM=4-methoxybenzyl) ether 48 with LiBH4 and the diastereoselective addition of sodium tert-butyl diazoacetate to

  描述了对角鲨烯合酶抑制剂泽拉果酸A和C的羰基内酯环加成方法。由D-酒石酸二叔丁酯（47）开始的十一步合成羰基叶立德前体8，该步骤涉及用LiBH4对单MPM（MPM = 4-甲氧基苄基）醚48进行区域选择性还原和非对映选择性加成的重氮乙酸叔丁酯钠制得α-酮酸酯10。在催化量的[Rh2（OAc）4]存在下，α-重氮酯8与3-丁炔-2-酮（40）反应得到所需产物。环加合物59为单个非对映异构体。烯酮59的二羟基化，随后进行顺序转化，可以构建功能齐全的2,8-二氧杂双环[3.2.1]辛烷核5。由5衍生的烯烃79是zaragozic酸A（1）和C（ 2），
• 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。