(2S,3R)-3-<(benzyloxy)methoxy>-2-methylpentanal | 123163-78-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3R)-3-<(benzyloxy)methoxy>-2-methylpentanal
• 英文别名: (2S,3R)-2-methyl-3-(phenylmethoxymethoxy)pentanal
• CAS: 123163-78-0
• 化学式: C₁₄H₂₀O₃
• 分子量: 236.311
• InChiKey: IPAXMCWYJOFKHR-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-<(benzyloxy)methoxy>-2-methylpentanal 在 溶剂黄146 、 lithium hexamethyldisilazane 、 tetramethylammonium triacetoxyborohydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 16.0h， 生成 (2S,3R,4R,6R,7S,8S,9R,10R,11R)-11-(benzyloxymethoxy)-1-O-tert-butyldimethylsilyl-3,4-(carbonyldioxy)-2,4,6,8,10-pentamethyldecane-1,7,9-triol
  参考文献：
  名称：

  全合成红霉素B

  摘要：

  我们报告了使用两种不同策略进行最终比赛时红霉素B首次完全合成的详细信息。这些方法中的第一种遵循经典方法，其中将去氨胺和可乐宁残基顺序连接到大环内酯上，该内酯是通过癸二酸衍生物的环化形成的，得到双糖基化大环内酯中间体，该中间体被转化为红霉素B.第二种策略的特征是一种非生物方法，其中将带有去氨胺残基的癸二酸环化，生成单糖基化的大环内酯，然后通过一系列步骤将其转化为红霉素B，所述步骤包括重新官能化和糖基化以引入可乐定。通过从头合成来制备双糖基化的癸二酸的尝试是失败的。关键癸二酸中间体的合成特征在于含有C（3）–C（10）的呋喃的氧化转化，以提供二氧杂双环[3.3.1]壬烯酮，该模板用作在C（6）上建立立体中心的模板）和C（8）。立体选择性羟醛反应用于建立C（11）-C（15）段，并进行立体选择性交联以引入包含C（1）-C（2）的丙酸酯亚基。

  DOI：

  10.1016/j.tet.2007.02.044
• 作为产物：
  描述：

  苄基氯甲基醚 在 N-甲基吗啉 、 锂硼氢 、 氯化亚砜 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 48.0h， 生成 (2S,3R)-3-<(benzyloxy)methoxy>-2-methylpentanal
  参考文献：
  名称：

  Strategies for Macrolide Synthesis. A Concise Approach to Protected Seco-Acids of Erythronolides A and B

  摘要：

  Concise syntheses of protected derivatives of the seco-acids of erythronolides A and B, 5 and 6, respectively, have been completed wherein the longest linear sequence requires only 13 chemical steps from 5-ethylfuraldehyde (15). The syntheses commenced with the asymmetric aldol condensation of 15 according to the Evans protocol to afford the optically pure syn adduct 16, thereby establishing the critical stereocenters at C(4) and C(5) of the erythromycin backbone. Reductive removal of the chiral auxiliary from 16 gave the diol 17, which was converted to the bicyclic enone 18 by an one-pot process involving sequential oxidation of the furan ring and acid-catalyzed bicycloketalization. Stereoselective elaboration of 18 to the tertiary alcohol 19 was achieved in two steps by sequential treatment with lithium dimethylcuprate and methyllithium in the presence of cerium trichloride. Compound 19 underwent facile acid-catalyzed reorganization to the isomeric ketal 21, which was transformed into 24 by a Swern oxidation and a second asymmetric aldol condensation. However, the necessary refunctionalization of 24 into a ketone that would participate in the requisite aldol reaction to append the C(11)-C(15) segment of the erythronolide backbone could not be induced. On the other hand, transthioketalization of 19 gave the triol 26, which was converted to 28 by the thermodynamically-controlled formation of an acetonide of the 1,2-diol array. Deprotection of the C(9) ketone function followed by Swern oxidation produced the keto aldehyde 31, which underwent chemoselective, Lewis acid-mediated addition of tri-n-butylcrotylstannane to the aldehyde function to furnish a mixture (4:1) of the homoallylic alcohols 32 and 33; the major product 32 comprises the C(1)-C(10) subunit common to the seco-acids of both erythronolides A and B. Diastereoselective aldol condensation of the enolate derived from 32 with 40 gave 42 as the major adduct; oxidative processing of the terminal olefin then delivered the erythronolide B seco-acid derivative 46. The proposed structure of 42 was initially based upon its conversion into the polyol 48, which was identical to that derived from natural erythronolide B (49). Subsequent to this chemical correlation, the X-ray structure of 50, which was prepared from 42, unequivocally verified this assignment. In experiments directed toward the preparation of the seco-acid of erythronolide A, the directed aldol reactions of 32 with the aldehydes 59 and 60 were examined. Although the addition of the enolate of 32 to 59 produced none of the requisite adduct, its reaction with 60 gave a mixture (1:5) of 62 and 64. Stereoselective reduction of the C(9) carbonyl function of 62 followed by oxidative cleavage of the double bond and global deprotection gave the polyol 62, which was identical with the polyol derived from natural erythromycin A (1).

  DOI：

  10.1021/ja00090a016

文献信息

• A concise asymmetric synthesis of the seco-acid of erythronolide B
  作者：Stephen F. Martin、Gregory J. Pacofsky、Ricky P. Gist、Wen Cherng Lee

  DOI：10.1021/ja00201a066

  日期：1989.9

  The concise synthesis of 3,a protected derivative of the seco acid of erythronolide B, has been achieved by a convergent approach wherein the longest linear sequence employs only 14 chemical operations with the total number of steps being 18. The approach is efficient, and substantial quantities of material may be prepared

  3，一种被保护的赤藓酮内酯 B 的二烯酸衍生物，通过收敛方法实现，其中最长的线性序列仅使用 14 个化学操作，总步数为 18。该方法有效且实质性可以准备大量的材料
• Effect of metal counterions on the stereoselectivity of aldol reactions used to assemble the seco acid backbone of erythromycin b
  作者：Stephen F. Martin、Wen-Cherng Lee

  DOI：10.1016/s0040-4039(00)73542-8

  日期：1993.4

  reactions of the enolates derived from the ketones 11, 15, and 19 with the aldehyde 2a depended upon whether the counterion was lithium or titanium. For lithium enolates the stereoselectivity appeared to be controlled by the stereochemistry alpha to the carbonyl group of the aldehyde partner, whereas the stereochemistry at the α′-carbon of the enolate was important for the titanium enolate.

  从酮衍生的烯醇化物的醛醇缩合反应的选择性diastereofacial 11，15，和19与醛2A依赖于抗衡离子是否锂或钛。对于烯醇锂而言，立体选择性似乎受α-醛配体的羰基的立体化学控制，而烯醇钛的α'-碳上的立体化学对于烯醇钛是重要的。
• The Asymmetric Synthesis of Erythromycin B
  作者：Stephen F. Martin、Tsuneaki Hida、Philip R. Kym、Michael Loft、Anne Hodgson

  DOI：10.1021/ja963575y

  日期：1997.4.1
• An Abiotic Strategy for the Enantioselective Synthesis of Erythromycin B
  作者：Paul J. Hergenrother、Anne Hodgson、Andrew S. Judd、Wen-Cherng Lee、Stephen F. Martin

  DOI：10.1002/anie.200351136

  日期：2003.7.21
• Synthesis and Biochemical Analysis of Complex Chain-Elongation Intermediates for Interrogation of Molecular Specificity in the Erythromycin and Pikromycin Polyketide Synthases
  作者：Jonathan D. Mortison、Jeffrey D. Kittendorf、David H. Sherman

  DOI：10.1021/ja9060596

  日期：2009.11.4

  The 6-deoxyerythronolide B synthase (DEBS) and pikromycin (Pik) polyketide synthase (PKS) are unique multifunctional enzyme systems that are responsible for the biosynthesis of the erythromycin and pikromycin 14-membered ring aglycones, respectively. Together, these natural product biosynthetic systems provide excellent platforms to examine the fundamental structural and catalytic elements that govern polyketide assembly, processing, and macrocyclization. In these studies, the native pentaketide intermediate for DEBS was synthesized and employed for in vitro chemoenzymatic synthesis of macrolactone products in engineered monomodules Ery5, Ery5-TE, and Ery6. A comparative analysis was performed with the corresponding Pik module 5 (PikAIII) and module 6 (PikAIV), dissecting key similarities and differences between these highly related PKSs. The data revealed that individual modules in the DEBS and Pik PKSs possess distinctive molecular selectivity profiles and suggest that substrate recognition has evolved unique characteristics in each system.