benzyl (2S)-3-[(2S,3R,4R,5R,6R)-3-azido-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydroxyoxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate | 218291-42-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: benzyl (2S)-3-[(2S,3R,4R,5R,6R)-3-azido-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydroxyoxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate
• CAS: 218291-42-0
• 化学式: C₃₇H₄₆N₄O₉Si
• 分子量: 718.879
• InChiKey: DJFOTSBVXQZGNC-AGAUYENESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-3-[(2S,3R,4R,5R,6R)-3-azido-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydroxyoxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate 、 Fuc2Ac3Ac4Ac(a1-2)Gal3Ac4Ac6Ac(b1-4)[Fuc2Ac3Ac4Ac(a1-3)]GlcNAc6Ac(b1-3)[Bz(-2)]Gal4Ac6Ac(b)-SEt 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 以82%的产率得到[(2R,3R,4S,5S,6R)-4-[(2S,3R,4R,5S,6R)-3-acetamido-6-(acetyloxymethyl)-5-[(2S,3R,4S,5S,6R)-4,5-diacetyloxy-6-(acetyloxymethyl)-3-[(2S,3S,4R,5R,6S)-3,4,5-triacetyloxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-4-[(2S,3S,4R,5R,6S)-3,4,5-triacetyloxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-acetyloxy-6-(acetyloxymethyl)-2-[(2R,3R,4R,5R,6S)-5-azido-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-6-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-oxo-3-phenylmethoxypropoxy]-3-hydroxyoxan-4-yl]oxyoxan-3-yl] benzoate
  参考文献：
  名称：

  Design and Synthesis of Le^y-Bearing Glycopeptides that Mimic Cell Surface Le^y Mucin Glycoprotein Architecture

  摘要：

  Five Lewis(y)-based glycopeptide anti-cancer vaccine candidates have been designed and synthesized to target tumor-associated cell-surface glycoprotein antigens and to improve the immunizing performance in comparison to related vaccines. The peptide backbone consisted of two regions, a glycodomain AcNH-SSS-and a nonglycosylated sequence,-AVAV-. The resultant glycopeptide was conjugated, via an additional spacer, to the lipid carrier PamCysSer. In this series of totally synthetic molecular vaccine candidates, one or three of the sequentially arranged serine residues were glycosylated. Furthermore, the Le(y) tetrasaccharide determinant region was kept constant while the internal glycan core was systematically varied. Glycal assembly was used to prepare the glycosyl donors, and two strategies were applied to provide the serine-O-linked polysaccharide domains. In the first approach, a protected serine derivative was attached directly to the fully elaborated glycan. Following this course, both alpha- and beta-Ser derivatives were accessed. In the second route, a GalNAc-alpha-Ser was joined with a glycosyl donor to afford exclusively the desired a-serine-linked product. The glycopeptides were assembled using iterative solution phase peptide coupling. Following global deprotection, the lipid carrier was then coupled to the glycopeptide, resulting in the targeted constructs. The synthesis of these molecular vaccine candidates constitutes an important advance that should enable rationalization of carbohydrate-induced immune response as well as identification of optimal Le(y)-based anti-cancer vaccine leads.

  DOI：

  10.1021/ja0011820
• 作为产物：
  描述：

  Fmoc-O-苄基-L-丝氨酸 在 咪唑 、 甲醇 、 三氟甲磺酸三甲基硅酯 、 碘 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl (2S)-3-[(2S,3R,4R,5R,6R)-3-azido-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydroxyoxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate
  参考文献：
  名称：

  Synthetic and Immunological Studies on Clustered Modes of Mucin-Related Tn and TF O-Linked Antigens:  The Preparation of a Glycopeptide-Based Vaccine for Clinical Trials against Prostate Cancer

  摘要：

  The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) and immunoconjugated to a carrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunological study. Three Tn conjugates were used to vaccinate groups of mice, and all preparations proved to be immunogenic. The Tn(c) covalently linked to KLH (27-KLH) plus the adjuvant QS-21 was the optimal vaccine, inducing high median IgM and IgG titers against Tn(c) by ELISA. These antibodies were strongly reactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancer cell Line LS-B by FAGS. The antibodies' reactivities with natural antigens were inhibited with synthetic Tn(c) but not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLH and 30-pam plus QS-21 are being tested in patients with prostate cancer.

  DOI：

  10.1021/ja9825128

文献信息

• A Broadly Applicable Method for the Efficient Synthesis of α-<i>O</i>-Linked Glycopeptides and Clustered Sialic Acid Residues
  作者：Jacob B. Schwarz、Scott D. Kuduk、Xiao-Tao Chen、Dalibor Sames、Peter W. Glunz、Samuel J. Danishefsky

  DOI：10.1021/ja9833265

  日期：1999.3.1

  The total syntheses of complex sialylated cell-surface antigens have been accomplished. The target systems include 2.3-STF, STn, 2,6-STF, and glycophorin antigens. In addition,an alpha-O-linked serine glycoside of an entire Lewis blood group (Y) antigen has been assembled.
• Probing Cell Surface “Glyco-Architecture” through Total Synthesis. Immunological Consequences of a Human Blood Group Determinant in a Clustered Mucin-like Context
  作者：Peter W. Glunz、Samuel Hintermann、Jacob B. Schwarz、Scott D. Kuduk、Xiao-Tao Chen、Lawrence J. Williams、Dalibor Sames、Samuel J. Danishefsky、Valery Kudryashov、Kenneth O. Lloyd

  DOI：10.1021/ja992309s

  日期：1999.11.1
• Synthetic and Immunological Studies on Clustered Modes of Mucin-Related Tn and TF O-Linked Antigens:  The Preparation of a Glycopeptide-Based Vaccine for Clinical Trials against Prostate Cancer
  作者：Scott D. Kuduk、Jacob B. Schwarz、Xiao-Tao Chen、Peter W. Glunz、Dalibor Sames、Govindaswami Ragupathi、Philip O. Livingston、Samuel J. Danishefsky

  DOI：10.1021/ja9825128

  日期：1998.12.1

  The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) and immunoconjugated to a carrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunological study. Three Tn conjugates were used to vaccinate groups of mice, and all preparations proved to be immunogenic. The Tn(c) covalently linked to KLH (27-KLH) plus the adjuvant QS-21 was the optimal vaccine, inducing high median IgM and IgG titers against Tn(c) by ELISA. These antibodies were strongly reactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancer cell Line LS-B by FAGS. The antibodies' reactivities with natural antigens were inhibited with synthetic Tn(c) but not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLH and 30-pam plus QS-21 are being tested in patients with prostate cancer.
• Design and Synthesis of Le^y-Bearing Glycopeptides that Mimic Cell Surface Le^y Mucin Glycoprotein Architecture
  作者：Peter W. Glunz、Samuel Hintermann、Lawrence J. Williams、Jacob B. Schwarz、Scott D. Kuduk、Valery Kudryashov、Kenneth O. Lloyd、Samuel J. Danishefsky

  DOI：10.1021/ja0011820

  日期：2000.8.1

  Five Lewis(y)-based glycopeptide anti-cancer vaccine candidates have been designed and synthesized to target tumor-associated cell-surface glycoprotein antigens and to improve the immunizing performance in comparison to related vaccines. The peptide backbone consisted of two regions, a glycodomain AcNH-SSS-and a nonglycosylated sequence,-AVAV-. The resultant glycopeptide was conjugated, via an additional spacer, to the lipid carrier PamCysSer. In this series of totally synthetic molecular vaccine candidates, one or three of the sequentially arranged serine residues were glycosylated. Furthermore, the Le(y) tetrasaccharide determinant region was kept constant while the internal glycan core was systematically varied. Glycal assembly was used to prepare the glycosyl donors, and two strategies were applied to provide the serine-O-linked polysaccharide domains. In the first approach, a protected serine derivative was attached directly to the fully elaborated glycan. Following this course, both alpha- and beta-Ser derivatives were accessed. In the second route, a GalNAc-alpha-Ser was joined with a glycosyl donor to afford exclusively the desired a-serine-linked product. The glycopeptides were assembled using iterative solution phase peptide coupling. Following global deprotection, the lipid carrier was then coupled to the glycopeptide, resulting in the targeted constructs. The synthesis of these molecular vaccine candidates constitutes an important advance that should enable rationalization of carbohydrate-induced immune response as well as identification of optimal Le(y)-based anti-cancer vaccine leads.