(3R,5S)-5-[(2R)-2-[(1R,3aR,4E,7aR)-4-[(2Z)-2-[(3S,5S)-3,5-二羟基-2-亚甲基-环己基亚基]乙亚基]-7a-甲基-2,3,3a,5,6,7-六氢-1H-茚-1-基]丙基]-3-羟基-3-甲基-四氢呋喃-2-酮 | 81203-50-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: (3R,5S)-5-[(2R)-2-[(1R,3aR,4E,7aR)-4-[(2Z)-2-[(3S,5S)-3,5-二羟基-2-亚甲基-环己基亚基]乙亚基]-7a-甲基-2,3,3a,5,6,7-六氢-1H-茚-1-基]丙基]-3-羟基-3-甲基-四氢呋喃-2-酮
• 中文别名: (5Z,7E)-(3S,23S,25R)-1,3β,25-三羟基-9,10-裂-5,7,10(19)-胆甾三烯桥-26,23-内酯
• 英文名称: (3R,5S)-5-((R)-2-((1R,3αS,7αR,E)-4-((Z)-2-((3S,5R)-3,5-dihydroxy-2-methylenecyclohexylidene)ethylidene)-7α-methyloctahydro-1H-inden-1-yl)propyl)-3-hydroxy-3-methyldihydrofuran-2(3H)-one
• 英文别名: (23S,25R)-1α,25-dihydroxyvitamin D₃ 26,23 lactone；(23S,25R)-1α,25-dihydroxyvitamin D3 26,23-lactone；Calcitriol Lactone；1,25-dihydroxyvitamin D3-26,23-lactone；(3R,5S)-5-[(2R)-2-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]propyl]-3-hydroxy-3-methyloxolan-2-one
• CAS: 81203-50-1
• 化学式: C₂₇H₄₀O₅
• 分子量: 444.612
• InChiKey: WMYIVSWWSRCZFA-RWVJFQLJSA-N

物化性质

• 沸点：
  624.1±55.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (22S,23R,25R)-1α,3β,25-trihydroxy-22-(phenylseleno)-5,7-cholestadiene 26,23-lactone 4-phenyl-1,2,4-triazoline-3,5-dione adduct 在 偶氮二异丁腈 、 三正丁基氢锡 、 potassium carbonate 作用下， 以 乙醇 、 二甲基亚砜 、 甲苯 、 苯 为溶剂， 反应 1.92h， 生成 (3R,5S)-5-[(2R)-2-[(1R,3aR,4E,7aR)-4-[(2Z)-2-[(3S,5S)-3,5-二羟基-2-亚甲基-环己基亚基]乙亚基]-7a-甲基-2,3,3a,5,6,7-六氢-1H-茚-1-基]丙基]-3-羟基-3-甲基-四氢呋喃-2-酮
  参考文献：
  名称：

  Facile stereoselective synthesis of (23S,25R)-1.alpha.,25-dihydroxyvitamin D3 26,23-lactone, a major metabolite of 1.alpha.,25-dihydroxyvitamin D3

  摘要：

  (23S,25R)-1-α,25-二羟基维生素D3 26,23-内酯（1a）是1-α,25-二羟基维生素D3的主要代谢物之一，它通过从1-α-羟基脱氢表雄酮（3）高效且有选择性地合成而得。首先，17-氧类固醇3通过以具有立体选择性的烯反应（ene reaction）为关键步骤，被转化为C(22)类固醇醛9，该反应保留了C(17)和C(20)位的天然立体化学。随后，9与具有正确立体化学以形成内酯（1a）的非对映异构C5硫酮4相结合。硫酮4可从商品化的(R)-柠檬苹果酸（R)-citramalic acid）中方便地制备。在具有γ-蜂碱（γ-collidine）的动态控制条件下，通过碘化内酯法，将Δ(22)-26-羧酸（16b）转化为侧链内酯，该内酯在C(23)位具有天然立体化学，且立体选择性高达84%。对类固醇Δ(22)-25-羟基-26-羧酸（16b、24和25）的碘化内酯化反应进行了详细研究，并提出了一种机制，其中C(25)位的构型和加入的吡啶碱起着重要作用。

  DOI：

  10.1021/jo00027a010

文献信息

• Process for the synthesis of vitamin d compounds and intermediates for the synthesis of the compounds
  申请人：Kashiwagi Hirotaka

  公开号：US20070135394A1

  公开（公告）日：2007-06-14

  An object of the present invention is to provide a process for synthesizing a vitamin D compound by simple procedures at lower costs. The present invention provides a process for preparing a vitamin D compound and an intermediate thereof, comprising the step of: (a) mixing a ketone or aldehyde, a Wittig reagent, and a base; or (b) mixing a ketone or aldehyde and a Wittig reagent, and then adding a base to the resulting mixture.

  本发明的一个目的是提供一种通过简单程序以更低成本合成维生素D化合物的方法。本发明提供了一种制备维生素D化合物及其中间体的方法，包括以下步骤：(a)混合酮或醛、威蒂格试剂和碱；或者(b)混合酮或醛和威蒂格试剂，然后向所得混合物中加入碱。
• [EN] COCRYSTALS OF STEROID AND SECOSTEROID COMPOUNDS AND COMPOSITIONS COMPRISING THEM<br/>[FR] CO-CRISTAUX DE COMPOSÉS STÉROÏDES ET SÉCOSTÉROÏDES ET COMPOSITIONS LES COMPRENANT
  申请人：CENTER FOR INTELLIGENT RES IN CRYSTAL ENGINEERING S L

  公开号：WO2021105147A1

  公开（公告）日：2021-06-03

  It is provided a cocrystal of a compound of formula (I) or of a compound formula (II) wherein X and Y are independently selected from -CH2- and -C(CH2)-, provided that al least one of X or Y is -CH2-; R1 is -CHCH3-Zm-Wn-(CH2)o-Tp-S, wherein Z is O, and m is 0 or 1; W is R4CH CHR5, wherein either R4 and R5 are H and the dashed line indicates that there is a single bond, or R4 and R5 together are forming a bond and the dashed line indicates that there is a double bond, and n is 0 or 1; o is 0, 1 or 3; T is selected from the group consisting of -CHR6-, -C(O), wherein R6 is -OH or -CH3, and p is 0 or 1; S is selected from the group consisting of H, (C1-C3) alkyl optionally substituted by -OH, (C1-C3) haloalkyl optionally substituted by -OH, cyclopropyl, or; and R2 is -H or -OH; R3 is H or CH3; and the dashed line in formula (II) indicates a single or a double bond; and a hydrogen bond donor coformer which is a phenolic compound. It is also provided a composition comprising the cocrystal and a personal care product comprising the composicion.

  提供了一种化合物的共晶体，该化合物具有公式（I）或化合物公式（II），其中X和Y独立地选自-CH2-和-C（CH2）-，前提是至少有一个X或Y是-CH2-；R1为-CHCH3-Zm-Wn-（CH2）o-Tp-S，其中Z为O，m为0或1；W为R4CH CHR5，其中R4和R5中的任何一个可以是H，虚线表示存在单键，或者R4和R5一起形成键，虚线表示存在双键，n为0或1；o为0，1或3；T从以下组中选择：-CHR6-，-C（O），其中R6为-OH或-CH3，p为0或1；S从以下组中选择：H，（C1-C3）烷基，可选地被-OH取代，（C1-C3）卤代烷基，可选地被-OH取代，环丙基，或；R2为-H或-OH；R3为H或CH3；公式（II）中的虚线表示单键或双键；以及作为氢键供体的辅体，其为酚类化合物。还提供了一种包含该共晶体的组合物和包含该组合物的个人护理产品。
• Stereoselective Synthesis of Four Calcitriol Lactone Diastereomers at C23 and C25
  作者：Akiko Nagata、Yusuke Akagi、Shadi Sedghi Masoud、Masahiro Yamanaka、Atsushi Kittaka、Motonari Uesugi、Minami Odagi、Kazuo Nagasawa

  DOI：10.1021/acs.joc.9b00403

  日期：2019.6.21

  (23S,25R)-Calcitriol lactone is a major metabolite of vitamin D3, but its synthesis has been far less well investigated than that of 1α,25(OH)2 vitamin D3, the active form of vitamin D3, even though the lactone is present at a significant level in serum. This paper describes stereoselective syntheses of natural calcitriol lactone and its diastereomers at C23 and C25. This work features (i) the diastereoselective

  （23小号，25 - [R ）-骨化三醇内酯是维生素d主要代谢产物3，但其合成已经比的1α远不如很好地研究，25（OH）2维生素d 3，维生素d活性形式3，即使内酯在血清中的含量很高。本文介绍了天然骨化三醇内酯及其非对映异构体在C23和C25的立体选择性合成。这项工作的特点是（i）在手性配体L2存在下，醛25的非对映选择性Reformatsky型crotylation，以构建C23的立体化学，以及（ii）均烯丙基-烯丙醇31的非对映选择性环氧化控制C25的立体化学。这些关键反应使我们能够与所有四种立体异构体合成CD环合成子30，并在钯（0）催化剂存在下通过与烯-炔型A环33反应将其进一步转化为骨化三醇内酯3a - 3d。。
• Total synthesis of 1.alpha.,25(R)-dihydroxy vitamin D3 26, 23(S)-lactone (calcitriol lactone), a natural metabolite of vitamin D3
  作者：Peter M. Wovkulich、Enrico G. Baggiolini、Bernard M. Hennessy、Milan R. Uskokovic、Eberhard Mayer、Anthony W. Norman

  DOI：10.1021/jo00171a068

  日期：1983.11
• A new insight into the role of rat cytochrome P450 24A1 in metabolism of selective analogs of 1α,25-dihydroxyvitamin D3
  作者：Steve Y. Rhieu、Andrew J. Annalora、Rose M. Gathungu、Paul Vouros、Milan R. Uskokovic、Inge Schuster、G. Tayhas R. Palmore、G. Satyanarayana Reddy

  DOI：10.1016/j.abb.2011.02.004

  日期：2011.5

  We examined the metabolism of two synthetic analogs of 1 alpha,25-dihydroxyvitamin D-3 (1), namely 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D-3 (2) and 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-dimethyl-vitamin D-3 (4) using rat cytochrome P450 24A1 (CYP24A1) in a reconstituted system. We noted that 2 is metabolized into a single metabolite identified as C26-hydroxy-2 while 4 is metabolized into two metabolites, identified as C26-hydroxy-4 and C26a-hydroxy-4. The structural modification of adding methyl groups to the side chain of 1 as in 4 is also featured in another analog, 1 alpha,25-dihydroxy-22,24-diene-24,26,27-tri-homo-vitamin D-3 (6). In a previous study, 6 was shown to be metabolized exactly like 4, however, the enzyme responsible for its metabolism was found to be not CYP24A1. To gain a better insight into the structural determinants for substrate recognition of different analogs, we performed an in silico docking analysis using the crystal structure of rat CYP24A1 that had been solved for the substrate-free open form. Whereas analogs 2 and 4 docked similar to 1,6 showed altered interactions for both the A-ring and side chain, despite prototypical recognition of the CD-ring. These findings hint that CYP24A1 metabolizes selectively different analogs of 1, based on their ability to generate discrete recognition cues required to close the enzyme and trigger the catalytic mechanism. 2011 Elsevier Inc. All rights reserved.