methyl 4,6-O-benzylidene-2-(tert-butyldimethylsilyloxy)-3-deoxy-3-[(3-pivaloyloxy)propyl]-α-D-altropyranoside | 769126-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: methyl 4,6-O-benzylidene-2-(tert-butyldimethylsilyloxy)-3-deoxy-3-[(3-pivaloyloxy)propyl]-α-D-altropyranoside
• 英文别名: methyl 4,6-O-benzylidene-2-O-tert-butyldimethylsilyl-3-deoxy-3-C-(3-pivaloyloxypropyl)-α-D-altropyranoside
• CAS: 769126-82-1
• 化学式: C₂₈H₄₆O₇Si
• 分子量: 522.755
• InChiKey: QKEMJZGALIJXGN-LUXCBIKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.85
• 重原子数：
  36.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  72.45
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 4,6-O-benzylidene-2-(tert-butyldimethylsilyloxy)-3-deoxy-3-[(3-pivaloyloxy)propyl]-α-D-altropyranoside 在 吡啶 、 2,6-二甲基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 三氟化硼乙醚 、 四丁基氟化铵 、 sodium cyanoborohydride 、 barium carbonate 、 锌 作用下， 以 四氢呋喃 、 丙醇 、 四氯化碳 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 45.5h， 生成 (3R,4R,5S)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-[3-{(tert-butyldimethylsilyl)oxy}propyl]oct-1-en-7-yne
  参考文献：
  名称：

  24,24-Dimethylvitamin D3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists

  摘要：

  Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1alpha-hydroxyvitamin D-3-26,23-lactones (8 and 9) and their C2alpha functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D-3 triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-alpha-methylene-gamma-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D-2. On the other hand, the A-ring enyne having 2alpha-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an omega-hydroxypropyl (8b and 9b) or an omega-hydroxypropoxyl group (8c and 9c) into the C2alpha position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.05.113
• 作为产物：
  描述：

  methyl 2,3-anhydro-4,6-O-benzilidene-α-D-mannopyranoside 在 吡啶 、 2,6-二甲基吡啶 、 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 52.0h， 生成 methyl 4,6-O-benzylidene-2-(tert-butyldimethylsilyloxy)-3-deoxy-3-[(3-pivaloyloxy)propyl]-α-D-altropyranoside
  参考文献：
  名称：

  24,24-Dimethylvitamin D3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists

  摘要：

  Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1alpha-hydroxyvitamin D-3-26,23-lactones (8 and 9) and their C2alpha functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D-3 triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-alpha-methylene-gamma-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D-2. On the other hand, the A-ring enyne having 2alpha-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an omega-hydroxypropyl (8b and 9b) or an omega-hydroxypropoxyl group (8c and 9c) into the C2alpha position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.05.113

文献信息

• The 2α-(3-hydroxypropyl) group as an active motif in vitamin D3 analogues as agonists of the mutant vitamin D receptor (Arg274Leu)
  作者：Shinobu Honzawa、Yasuhiro Yamamoto、Atsushi Yamashita、Takayuki Sugiura、Masaaki Kurihara、Midori A. Arai、Shigeaki Kato、Atsushi Kittaka

  DOI：10.1016/j.bmc.2007.12.039

  日期：2008.3.15

  We designed and synthesized 1 alpha- and 1 beta-hydroxymethyl-2 alpha-(3-hydroxypropyl)-25-hydroxyvitamin D-3 (2a,b) and related analogues 2 alpha-(3-hydroxypropyl)-25-hydroxyvitamin D-3 (3), Posner's analogues of 1 alpha- and 1 beta-hydroxymethyl-25-hydroxyvitamin D-3 (4a,b), as well as 2 alpha-(3-hydroxypropyl)-1 alpha,25-dihydroxyvitamin D-3 (5), to confirm the effect of the 1 alpha-hydroxy group and/or 2 alpha-(3-hydroxypropyl) group of vitamin D-3 analogues with the modified A-ring moiety on the mutant vitamin D receptor, VDR(Arg274Leu). The 2 alpha-(3-hydroxypropyl) group showed better effect on enhancement of the transcriptional activity through the mutant VDR than the 1 alpha- and 1 beta-hydroxymethyl groups. (C) 2007 Elsevier Ltd. All rights reserved.