(2R,3R)-tert-butyl 3-hydroxy-2-tetradecyloctadecanoate | 932394-87-1

• 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: (2R,3R)-tert-butyl 3-hydroxy-2-tetradecyloctadecanoate
• 英文别名: tert-butyl (2R,3R)-3-hydroxy-2-tetradecyloctadecanoate
• CAS: 932394-87-1
• 化学式: C₃₆H₇₂O₃
• 分子量: 552.966
• InChiKey: JSELJSJZROOXBG-KKLWWLSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.6
• 重原子数：
  39
• 可旋转键数：
  31
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,3R)-tert-butyl 3-hydroxy-2-tetradecyloctadecanoate 在 三乙基硅烷 、 三氟甲磺酸三甲基硅酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.75h， 生成 (2R,3R)-3-benzyloxy-2-tetradecyloctadecanoic acid
  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：

  tert-butyl 3-oxooctadecanoate 在 [(S)-2,2'-双(二苯基磷)-1,1'-联萘]二氯化钌(II) 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， -48.0 ℃ 、6.86 MPa 条件下， 反应 78.5h， 生成 (2R,3R)-tert-butyl 3-hydroxy-2-tetradecyloctadecanoate
  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

• Development of Vizantin, a Safe Immunostimulant, Based on the Structure–Activity Relationship of Trehalose-6,6′-dicorynomycolate
  作者：Hirofumi Yamamoto、Masataka Oda、Mayo Nakano、Naoyuki Watanabe、Kenta Yabiku、Masahiro Shibutani、Masahisa Inoue、Hiroshi Imagawa、Masahiro Nagahama、Seiichiro Himeno、Kojun Setsu、Jun Sakurai、Mugio Nishizawa

  DOI：10.1021/jm3016443

  日期：2013.1.10

  Vizantin, 6,6'-bis-O-(3-nonyldodecanoy1)-alpha,alpha'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.