N-(9-fluorenylmethyloxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester | 100938-55-4

• 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
• 英文名称: N-(9-fluorenylmethyloxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester
• 英文别名: N-Fmoc-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester；N-(fluoren-9-ylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester；N-(fluoren-9-ylmethoxycarbonyl)-(2-azido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threonine benzyl ester；N-(9H-fluorene-9-yl)-methoxycarbonyl-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester；benzyl (2S,3R)-3-[(2S,3R,4R,5R,6R)-4,5-diacetyloxy-6-(acetyloxymethyl)-3-azidooxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoate
• CAS: 100938-55-4
• 化学式: C₃₈H₄₀N₄O₁₂
• 分子量: 744.755
• InChiKey: SVGXCNOZZUJQAW-NXSUXUFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  54
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  176
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-(9-fluorenylmethyloxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester 在 Rh on carbon 吡啶 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 N-(fluoren-9-ylmethoxycarbonyl)-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threonine benzyl ester
  参考文献：
  名称：

  The effects of glycosylation on peptide backbone conformation

  摘要：

  DOI：

  10.1021/ja00061a053
• 作为产物：
  描述：

  D-(+)-galactosamine hydrochloride 在 吡啶 、 4 A molecular sieve 、 triflic azide 、 碘 、 potassium carbonate 、 copper(II) sulfate 、 六甲基二硅氮烷 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 22.0h， 生成 N-(9-fluorenylmethyloxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester
  参考文献：
  名称：

  Iodine Promoted Glycosylation with Glycosyl Iodides: α‐Glycoside Synthesis

  摘要：

  Glycosidation of fully acetylated glucopyranosyl iodide with methanol under the influence of iodine gave a-glucoside selectively. Use of less reactive acceptors led to the formation of alpha/beta-mixtures. Glycosylations with fully benzoylated glucosyl iodide yielded beta-glucosides only. In contrast, iodine-promoted glycosylation of serine and threonine with 2-azido-2-deoxy-glycosyl iodides, easily obtained in three steps, proceeded smoothly, resulting in only alpha-linked products in high yield in most cases.

  DOI：

  10.1081/car-200067028

文献信息

• Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen-based anti-cancer vaccine candidates
  作者：Mingjing Li、Fan Yu、Chao Yao、Peng George Wang、Yonghui Liu、Wei Zhao

  DOI：10.1039/c7ob02976d

  日期：——

  Therapeutic vaccines have been regarded as a very promising treatment modality against cancer. Tumor-associated MUC1 is a promising antigen for the design of antitumor vaccines. However, body's immune tolerance and low immunogenicity of MUC1 glycopeptides limited their use as effective antigen epitopes of therapeutic vaccines. To solve this problem, we chose the immune dominant region of MUC1 VNTRs

  治疗性疫苗被认为是一种非常有前途的抗癌治疗方法。肿瘤相关性MUC1是用于设计抗肿瘤疫苗的有前途的抗原。但是，人体的免疫耐受性和MUC1糖肽的低免疫原性限制了它们作为治疗性疫苗的有效抗原表位的用途。为了解决这个问题，我们选择了MUC1 VNTRs的免疫优势区域。我们设计并合成了其线性三价糖肽片段，并将其与BSA偶联。免疫学评估表明，基于糖基化MUC1的疫苗11诱导的抗体比未糖基化10的抗体具有更强的结合力。新型构建的抗原表位具有克服天然MUC1糖肽弱免疫原性的潜力，值得进一步研究。
• A Synthetic MUC1 Glycopeptide Bearing βGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells
  作者：Vanessa Leiria Campo、Thalita B. Riul、Leandro Oliveira Bortot、Maristela B. Martins-Teixeira、Marcelo Fiori Marchiori、Emanuela Iaccarino、Menotti Ruvo、Marcelo Dias-Baruffi、Ivone Carvalho

  DOI：10.1002/cbic.201600473

  日期：2017.3.16

  Anticancer immunogenicity: Glycopeptides incorporating αGalNAc‐Thr (Tn) and βGalNAc‐Thr residues as Tn antigen isomers were synthesized as mimetics of MUC1 tumor mucin glycoproteins. The unnatural βGalNAc‐glycopeptide‐BSA showed improved immunogenicity, with potential for the development of anticancer vaccines.

  抗癌免疫原性：糖肽结合了αGalNAc-Thr（Tn）和βGalNAc-Thr残基作为Tn抗原异构体，被合成为MUC1肿瘤粘蛋白糖蛋白的模拟物。非天然的βGalNAc-糖肽-BSA具有改善的免疫原性，具有开发抗癌疫苗的潜力。
• Synthesis of glycopeptides with the TN and T antigen structures, and their coupling to bovine serum albumin
  作者：Horst Kunz、Stefan Birnbach、Peter Wernig

  DOI：10.1016/0008-6215(90)84081-5

  日期：1990.7

  O-glycosyl-serine and -threonine linkages were stable. Ester groups were removed from the carbohydrate moieties with methanolic hydrazine, to give the TN and T antigen glycopeptides which were coupled to bovine serum albumin (BSA) via a carbodi-imide procedure and without any spacer groups. The resulting conjugates contained an average of greater than 20 glycopeptides per protein molecule. They are not

  合成了具有TN和T抗原结构的糖肽，这些肽代表具有血型M特异性的去唾液酸糖蛋白的N端三肽，已使用芴基甲氧基羰基（Fmoc）和2-吡啶基乙氧基羰基（Pyoc）基团进行氨基保护，并使用苄基酯作为羧基封闭基团来合成糖肽功能。Fmoc和Pyoc基团可以通过在碱敏感的O-糖基丝氨酸和-苏氨酸键稳定的条件下用弱碱吗啉处理而除去。用甲醇肼从碳水化合物部分除去酯基，得到TN和T抗原糖肽，其通过碳二亚胺方法与牛血清白蛋白（BSA）偶联，并且没有任何间隔基。所得的缀合物每个蛋白质分子平均包含大于20个糖肽。
• Highly Efficient Stereospecific Preparation of Tn and TF Building Blocks Using Thioglycosyl Donors and the Ph 2 SO/Tf 2 O Promotor System*
  作者：David Cato、Therese Buskas、Geert‐Jan Boons

  DOI：10.1081/car-200067091

  日期：2005.8.1

  The activation of 2‐azido‐2‐deoxy Tn and TF thioglycosyl donors by the powerful thiophilic promoter system Ph2SO/Tf2O has been investigated. Glycosylation of an Fmoc‐protected threonine derivative gave 1,2‐cis glycosides in high yields and excellent stereoselectivities. The galactosylation of phenyl 2‐azido‐4,6‐O‐benzylidene‐2‐deoxy‐1‐thio‐β‐D‐galactopyranoside was achieved in high yield and without

  已经研究了强大的亲硫性启动子系统Ph2SO / Tf2O对2-叠氮基-2-脱氧Tn和TF硫糖基供体的活化作用。Fmoc保护的苏氨酸衍生物的糖基化可以高产率和出色的立体选择性得到1,2-顺式糖苷。苯基2-叠氮基-4,6-O-苄叉基-2-脱氧-1-硫代-β-D-吡喃半乳糖苷的半乳糖基化反应是高收率的，使用携带有2-O-（2的三氯乙酰胺基供体不会形成原酸酯。 ，5-二氟苯甲酰基）基团。可以通过van Boom启动子直接激活所构建的TF二糖的异头噻吩基，以实现苏氨酸衍生物的糖基化。*献给Jacques H. van Boom教授
• 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.