(7S)-2,7-脱水-3,4-二-C-羧基-8,9,10,12,13-五脱氧-10-亚甲基-12-(苯基甲基)-L-赤式-L-甘油-D-阿卓-7-十三碳酮-7,4-呋喃并音波酸11-乙酸酯5-[(2E,4S,6S)-4,6-二甲基-2-辛烯酸酯] | 142561-96-4

• 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
• 中文名称: (7S)-2,7-脱水-3,4-二-C-羧基-8,9,10,12,13-五脱氧-10-亚甲基-12-(苯基甲基)-L-赤式-L-甘油-D-阿卓-7-十三碳酮-7,4-呋喃并音波酸11-乙酸酯5-[(2E,4S,6S)-4,6-二甲基-2-辛烯酸酯]
• 中文别名: 萨拉哥酸A
• 英文名称: zaragozic acid A
• 英文别名: squalestatin 1；squalestatin；zaragozic acid；(1S,3S,4S,5R,6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-[(E,4S,6S)-4,6-dimethyloct-2-enoyl]oxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid
• CAS: 142561-96-4
• 化学式: C₃₅H₄₆O₁₄
• 分子量: 690.742
• InChiKey: DFKDOZMCHOGOBR-NCSQYGPNSA-N

物化性质

• 比旋光度：
  D22 +18.3° (c = 0.60 in CHCl3); D25 +37° (c = 1.29 in methanol)
• 沸点：
  850.1±65.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  49
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  223
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (7S)-2,7-脱水-3,4-二-C-羧基-8,9,10,12,13-五脱氧-10-亚甲基-12-(苯基甲基)-L-赤式-L-甘油-D-阿卓-7-十三碳酮-7,4-呋喃并音波酸11-乙酸酯5-[(2E,4S,6S)-4,6-二甲基-2-辛烯酸酯] 在 咪唑 、 2,4,6-三甲基吡啶 、 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 N-羟基丁二酰亚胺 、 sodium azide 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.92h， 生成 ditert-butyl (1S,3R,4S,5R,6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-3-(aminomethyl)-7-[tert-butyl(dimethyl)silyl]oxy-6-[(E,4S,6S)-4,6-dimethyloct-2-enoyl]oxy-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylate
  参考文献：
  名称：

  The Squalestatins:  Inhibitors of Squalene Synthase. Enzyme Inhibitory Activities and in Vivo Evaluation of C3-Modified Analogues

  摘要：

  Squalestatin analogues modified at C3 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase in vitro. While the 4,6-dimethyloctenoate ester group at C6 was maintained, a number of modifications to the C3 carboxylic acid were well tolerated. However, in the absence of the C6 ester group, similar modifications to the C3 carboxyl group caused loss of activity. Selected compounds were evaluated for their ability to inhibit cholesterol biosynthesis in vivo in rats 1 and 6 h postadministration. Analogues of squalestatin 1 (S1) modified at C3 were found to possess a shorter duration of effect in vivo which is reflected in their substantially reduced ability to lower serum cholesterol levels in marmosets. Significant cholesterol lowering (up to 62%) for the C3 hydroxymethyl analogue Ib was observed only; when this compound was dosed three times a day for 3 days.

  DOI：

  10.1021/jm950893j
• 作为产物：
  描述：

  tri-tert-butyl [1S,1(4S,5R),3S,4S,5R,6R,7R]-6-acetoxy-1-(4-acetoxy-5-methyl-3-methylene-6-phenylhexyl)-7-(tert-butoxycarbonyl)oxy-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate 在 4-二甲氨基吡啶 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 (7S)-2,7-脱水-3,4-二-C-羧基-8,9,10,12,13-五脱氧-10-亚甲基-12-(苯基甲基)-L-赤式-L-甘油-D-阿卓-7-十三碳酮-7,4-呋喃并音波酸11-乙酸酯5-[(2E,4S,6S)-4,6-二甲基-2-辛烯酸酯]
  参考文献：
  名称：

  通过羰基内酯环加成策略合成zaragozic酸A和C。

  摘要：

  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），

  DOI：

  10.1002/chem.200601212

文献信息

• [EN] METHODS FOR PRODUCING D-TRYPTOPHAN AND SUBSTITUTED D-TRYPTOPHANS<br/>[FR] PROCÉDÉS DE PRODUCTION DE D-TRYPTOPHANE ET DE D-TRYPTOPHANES SUBSTITUÉS
  申请人：UNIV CALIFORNIA

  公开号：WO2021055696A1

  公开（公告）日：2021-03-25

  Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acids in both primary and secondary metabolism; and are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. As disclosed herein, we show that IvoA catalyzes ATP-dependent unidirectional stereoinversion of L-tryptophan to D-tryptophan with complete conversion. While the stereoinversion is catalyzed by the epimerization (E) domain, the terminal condensation (C) domain stereoselectively hydrolyzes D-tryptophanyl-S-phosphopantetheine thioester and thus represents a noncanonical C domain function. Using IvoA, we demonstrate a biocatalytic stereoinversion/deracemization route to access a variety of substituted D-tryptophan analogs in high enantiomeric excess.

  单模块非核糖体肽合酶（NRPSs）和类NRPS酶在初级和次级代谢中激活和转化羧酸，由于其生物催化潜力，备受关注。单模块NRPS IvoA 对真菌色素生物合成至关重要。正如本文所披露的，我们展示了IvoA 催化ATP依赖的L-色氨酸向D-色氨酸的单向立体反转，实现了完全转化。虽然立体反转由外消旋（E）结构域催化，但末端缩合（C）结构域具有立体选择性地水解D-色氨酰-S-磷酰巯基丝氨酸酯，因此代表了非规范的C结构域功能。利用IvoA，我们展示了一种生物催化的立体反转/去消旋途径，以获得多种取代D-色氨酸类似物，其旋光异构体过量达到高水平。
• Heterocycles as nicotinic acid receptor agonists for the treatment of dyslipidemia
  申请人：Palani Anandan

  公开号：US20060264489A1

  公开（公告）日：2006-11-23

  A compound having the general structure of Formula (I): or a pharmaceutically acceptable salt, solvate, ester, or tautomer thereof, wherein: Q is selected from the group consisting of: and L is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, ester, or tautomer thereof, are useful in treating diseases, disorders, or conditions such as metabolic syndrome and dyslipidemia.

  具有通式（I）的一种化合物： 或其药学上可接受的盐、溶剂化合物、酯或互变异构体，其中： Q选自以下群组： 和 L选自以下群组： 或其药学上可接受的盐、溶剂化合物、酯或互变异构体，可用于治疗代谢综合征和血脂异常等疾病、疾患或症状。
• Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions
  申请人：Graziano P. Michael

  公开号：US20050096307A1

  公开（公告）日：2005-05-05

  The present invention provides compositions, therapeutic combinations and methods including: (a) at least one lipid modulating agent; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity and lowering plasma levels of sterols or 5α-stanols.

  本发明提供了包括以下内容的组合物、治疗组合和方法：(a)至少一种脂质调节剂；和(b)至少一种取代的噁唑烷酮或取代的β-内酰胺甾醇吸收抑制剂，可用于治疗血管疾病、糖尿病、肥胖以及降低血浆中甾醇或5α-甾烷醇的水平。
• Combinations of substituted azetidinones and CB1 antagonists
  申请人：Veltri P. Enrico

  公开号：US20060069080A1

  公开（公告）日：2006-03-30

  The present invention provides compositions, therapeutic combinations and methods including: (a) at least one selective CB 1 antagonist; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity, metabolic syndrome and lowering plasma levels of sterols or 5α-stanols.

  本发明提供了包括以下内容的组合物、治疗组合和方法：(a)至少一种选择性CB1拮抗剂；和(b)至少一种取代的氮杂环丁烷或取代的β-内酰胺甾醇吸收抑制剂，可用于治疗血管疾病、糖尿病、肥胖、代谢综合征以及降低血浆中的甾醇或5α-甾烷醇水平。
• [EN] DIPHENYLAZETIDINONE DERIVATES PROCESSING CHOLESTEROL ABSORPTION INHIBITORY ACTIVITY<br/>[FR] DERIVES DIPHENYLAZETIDINONE PRESENTANT UNE ACTIVITE D'INHIBITION D'ABSORPTION DU CHOLESTEROL
  申请人：ASTRAZENECA AB

  公开号：WO2005061451A1

  公开（公告）日：2005-07-07

  Compounds of formula (XV): [Chemical formula should be inserted here. Please see paper copy] (XV) (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  公式（XV）的化合物：[应在此处插入化学公式。请参见纸质副本]（XV）（其中变量组如内部定义）药物可接受的盐、溶剂化物、这些盐的溶剂化物和前药及其用作治疗高脂血症的胆固醇吸收抑制剂。还描述了它们的制造过程和含有它们的药物组合物。