6,6'-bis-O-[(2R,3R)-3-benzyloxy-2-tetradecyloctadecanoyl]-2,3,4,2',3',4'-hexabenzyl-α,α'-trehalose

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: 6,6'-bis-O-[(2R,3R)-3-benzyloxy-2-tetradecyloctadecanoyl]-2,3,4,2',3',4'-hexabenzyl-α,α'-trehalose
• 英文别名: [(2R,3R,4S,5R,6R)-3,4,5-tris(phenylmethoxy)-6-[(2R,3R,4S,5R,6R)-3,4,5-tris(phenylmethoxy)-6-[[(2R,3R)-3-phenylmethoxy-2-tetradecyloctadecanoyl]oxymethyl]oxan-2-yl]oxyoxan-2-yl]methyl (2R,3R)-3-phenylmethoxy-2-tetradecyloctadecanoate
• 化学式: C₁₃₂H₁₉₄O₁₅
• 分子量: 2020.98
• InChiKey: HIXVJWLJPHZXCG-RRKRDHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  41.1
• 重原子数：
  147
• 可旋转键数：
  90
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  154
• 氢给体数：
  0
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  6,6'-bis-O-[(2R,3R)-3-benzyloxy-2-tetradecyloctadecanoyl]-2,3,4,2',3',4'-hexabenzyl-α,α'-trehalose 在 palladium hydroxide - carbon 氢气 作用下， 以 甲醇 、 氯仿 为溶剂， 20.0 ℃ 、101.32 kPa 条件下， 反应 7.0h， 以94%的产率得到6,6'-二((2R,3R)-3-羟基-2-十四烷基十八烷酸酯)-海藻糖
  参考文献：
  名称：

  Efficient Syntheses of a Series of Trehalose Dimycolate (TDM)/Trehalose Dicorynomycolate (TDCM) Analogues and Their Interleukin-6 Level Enhancement Activity in Mice Sera

  摘要：

  We found an IL-6 level-enhancing compound during our synthetic study of trehalose-6,6'-dimycolate (1, TDM, formerly called cord factor) analogues. TDM is a glycolipid distributed in the cell wall of Mycobacterium tuberculosis and shows significant antitumor activity based on an immunoadjuvant activity. However, due to its significant toxicity, TDM is not yet applicable for practical use. In 1993, Datta and Takayama reported the purification of trehalose-6,6'-dicorynomycolate (2c, TDCM) from Corynebacterium spp. We have previously reported the synthesis of four diastereomeric TDCMs and showed that the synthetic (2R,3R,2'R,3'R)-TDCM (2c, hereafter abbreviated RRRR-TDCM-C-14) is identical to natural TDCM; we also demonstrated that 2c and SSSS-TDCM-C-14 (3c) showed significant antitumor activity as well as inhibitory activity in experimental lung metastasis based on the immunoadjuvant activity. Furthermore, we found that the significant lethal toxicity in mice by TDM (1) was no longer observed with the shorter-chain analogues of TDCMs. Therefore, we have elucidated that the 2,3-antistereochemistry (RR or SS) of the fatty acid residue is promising for biological activities. The chain length of the fatty acid residue should also be important for the biological activity, and thus, we designed a general synthetic procedure for trehalose diesters with 2,3-antistereochemistry and a series of chain lengths by using Noyori's asymmetric reduction of beta,beta-ketoesters followed by antiselective alkylation according to Frater to give beta,beta-hydroxy alcohols as the key steps. Thus, we prepared trehalose diesters (TDCM) 2a-d, 3a-d, and 4a-d as well as monoesters (TMCM) 5a-d and 6a-d. Immunological activities of TDCMs and TMCMs were evaluated by determining IL-6 level enhancement in mouse serum, and we found that RRRR-TDCM-C-14 (2c) and RRSS-TDCM-C-14 (4c) showed significant IL-6 level enhancement activities.

  DOI：

  10.1021/jo062018j
• 作为产物：
  描述：

  [(2R,3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-6-((2R,3R,4S,5R,6R)-3,4,5-tris-benzyloxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yl]-methanol 、 (2R,3R)-3-benzyloxy-2-tetradecyloctadecanoic acid 在 4-二甲氨基吡啶 、 4 A molecular sieve 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 以50%的产率得到6,6'-bis-O-[(2R,3R)-3-benzyloxy-2-tetradecyloctadecanoyl]-2,3,4,2',3',4'-hexabenzyl-α,α'-trehalose
  参考文献：
  名称：

  Efficient Syntheses of a Series of Trehalose Dimycolate (TDM)/Trehalose Dicorynomycolate (TDCM) Analogues and Their Interleukin-6 Level Enhancement Activity in Mice Sera

  摘要：

  We found an IL-6 level-enhancing compound during our synthetic study of trehalose-6,6'-dimycolate (1, TDM, formerly called cord factor) analogues. TDM is a glycolipid distributed in the cell wall of Mycobacterium tuberculosis and shows significant antitumor activity based on an immunoadjuvant activity. However, due to its significant toxicity, TDM is not yet applicable for practical use. In 1993, Datta and Takayama reported the purification of trehalose-6,6'-dicorynomycolate (2c, TDCM) from Corynebacterium spp. We have previously reported the synthesis of four diastereomeric TDCMs and showed that the synthetic (2R,3R,2'R,3'R)-TDCM (2c, hereafter abbreviated RRRR-TDCM-C-14) is identical to natural TDCM; we also demonstrated that 2c and SSSS-TDCM-C-14 (3c) showed significant antitumor activity as well as inhibitory activity in experimental lung metastasis based on the immunoadjuvant activity. Furthermore, we found that the significant lethal toxicity in mice by TDM (1) was no longer observed with the shorter-chain analogues of TDCMs. Therefore, we have elucidated that the 2,3-antistereochemistry (RR or SS) of the fatty acid residue is promising for biological activities. The chain length of the fatty acid residue should also be important for the biological activity, and thus, we designed a general synthetic procedure for trehalose diesters with 2,3-antistereochemistry and a series of chain lengths by using Noyori's asymmetric reduction of beta,beta-ketoesters followed by antiselective alkylation according to Frater to give beta,beta-hydroxy alcohols as the key steps. Thus, we prepared trehalose diesters (TDCM) 2a-d, 3a-d, and 4a-d as well as monoesters (TMCM) 5a-d and 6a-d. Immunological activities of TDCMs and TMCMs were evaluated by determining IL-6 level enhancement in mouse serum, and we found that RRRR-TDCM-C-14 (2c) and RRSS-TDCM-C-14 (4c) showed significant IL-6 level enhancement activities.

  DOI：

  10.1021/jo062018j

文献信息

• Efficient Syntheses of a Series of Trehalose Dimycolate (TDM)/Trehalose Dicorynomycolate (TDCM) Analogues and Their Interleukin-6 Level Enhancement Activity in Mice Sera
  作者：Mugio Nishizawa、Hirofumi Yamamoto、Hiroshi Imagawa、Véronique Barbier-Chassefière、Emmanuel Petit、Ichiro Azuma、Dulce Papy-Garcia

  DOI：10.1021/jo062018j

  日期：2007.3.1

  We found an IL-6 level-enhancing compound during our synthetic study of trehalose-6,6'-dimycolate (1, TDM, formerly called cord factor) analogues. TDM is a glycolipid distributed in the cell wall of Mycobacterium tuberculosis and shows significant antitumor activity based on an immunoadjuvant activity. However, due to its significant toxicity, TDM is not yet applicable for practical use. In 1993, Datta and Takayama reported the purification of trehalose-6,6'-dicorynomycolate (2c, TDCM) from Corynebacterium spp. We have previously reported the synthesis of four diastereomeric TDCMs and showed that the synthetic (2R,3R,2'R,3'R)-TDCM (2c, hereafter abbreviated RRRR-TDCM-C-14) is identical to natural TDCM; we also demonstrated that 2c and SSSS-TDCM-C-14 (3c) showed significant antitumor activity as well as inhibitory activity in experimental lung metastasis based on the immunoadjuvant activity. Furthermore, we found that the significant lethal toxicity in mice by TDM (1) was no longer observed with the shorter-chain analogues of TDCMs. Therefore, we have elucidated that the 2,3-antistereochemistry (RR or SS) of the fatty acid residue is promising for biological activities. The chain length of the fatty acid residue should also be important for the biological activity, and thus, we designed a general synthetic procedure for trehalose diesters with 2,3-antistereochemistry and a series of chain lengths by using Noyori's asymmetric reduction of beta,beta-ketoesters followed by antiselective alkylation according to Frater to give beta,beta-hydroxy alcohols as the key steps. Thus, we prepared trehalose diesters (TDCM) 2a-d, 3a-d, and 4a-d as well as monoesters (TMCM) 5a-d and 6a-d. Immunological activities of TDCMs and TMCMs were evaluated by determining IL-6 level enhancement in mouse serum, and we found that RRRR-TDCM-C-14 (2c) and RRSS-TDCM-C-14 (4c) showed significant IL-6 level enhancement activities.