(20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3-on | 145573-34-8

• 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
• 英文名称: (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3-on
• 英文别名: [(2S)-2-[(8S,9S,10R,13S,14S,17R)-10,13-dimethyl-3-oxo-4,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]propyl] 4-methylbenzenesulfonate
• CAS: 145573-34-8
• 化学式: C₂₉H₃₈O₄S
• 分子量: 482.684
• InChiKey: PMKQBKJCACRGNT-RQZMLCOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3-on 在 sodium tetrahydroborate 、 calcium chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.5h， 以80%的产率得到(20S)-20-(p-toluenesulfonyloxymethyl)pregna-1,5-dien-3β-ol
  参考文献：
  名称：

  Umwandlung von (20S)-20-(Hydroxymethyl)pregna-1,4-dien-3-on in (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3?-ol und -3?-ol: Zwischenprodukte f�r Vitamin D-Derivate

  摘要：

  Efficient three-step approaches to the two 3-epimeric 22-tosylated 1,5-diene-3,22-diols 6 and 7 starting with (20S)-20-(hydroxymethyl)pregna-1,4-dien-3-one (1) were developed and optimized. Isomerization of 1 to the 1,5-dien-3-one 3 and subsequent tosylation furnished the deconjugated 3-ketone 4. The 3 beta-alcohol 6 was available from 4 by means of in situ generated calcium borohydride. Treatment of 4 with lithium trisiamylborohydride (LS-Selectride) afforded the highest yield of the hitherto unknown 3 alpha-epimer 7. Following the optimized synthesis, 6 and 7 were obtained from 1 in 60% and 50% overall yield, respectively.

  DOI：

  10.1002/prac.19963380145
• 作为产物：
  描述：

  (20S)-20-(hydroxymethyl)pregna-1,4-dien-3-one 、 二甲基亚砜 在 potassium tert-butylate 、 对甲苯磺酰氯 作用下， 生成 (20S)-20-(Methylthiomethyloxymethyl)pregna-1,5-dien-3-on 、 (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,4-dien-3-on 、 (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3-on
  参考文献：
  名称：

  Umwandlung von (20S)-20-(Hydroxymethyl)pregna-1,4-dien-3-on in (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3?-ol und -3?-ol: Zwischenprodukte f�r Vitamin D-Derivate

  摘要：

  Efficient three-step approaches to the two 3-epimeric 22-tosylated 1,5-diene-3,22-diols 6 and 7 starting with (20S)-20-(hydroxymethyl)pregna-1,4-dien-3-one (1) were developed and optimized. Isomerization of 1 to the 1,5-dien-3-one 3 and subsequent tosylation furnished the deconjugated 3-ketone 4. The 3 beta-alcohol 6 was available from 4 by means of in situ generated calcium borohydride. Treatment of 4 with lithium trisiamylborohydride (LS-Selectride) afforded the highest yield of the hitherto unknown 3 alpha-epimer 7. Following the optimized synthesis, 6 and 7 were obtained from 1 in 60% and 50% overall yield, respectively.

  DOI：

  10.1002/prac.19963380145

文献信息

• AUSGANGSVERBINDUNGEN ZUR HERSTELLUNG VON CALCITRIOL SOWIE DESSEN ABKÖMMLINGEN, VERFAHREN ZUR HERSTELLUNG DIESER AUSGANGSVERBINDUNGEN SOWIE ZWISCHENPRODUKTE FÜR DIESES VERFAHREN
  申请人：JENAPHARM GmbH

  公开号：EP0572489A1

  公开（公告）日：1993-12-08
• [EN] STARTING COMPOUNDS FOR PREPARING CALCITRIOL AND ITS DERIVATIVES, METHOD FOR PREPARING THESE STARTING COMPOUNDS AND INTERMEDIATE PRODUCTS FOR THIS METHOD
  申请人：——

  公开号：WO1992014746A1

  公开（公告）日：1992-09-03

  [FR] Il est décrit de nouveaux composés de départ pour la fabrication de calcitriol (1alpha, 25-dihydroxycholecalciférol) et de ses dérivés présentant, comparativement au calcitriol, des modifications, notamment dans la chaîne latérale C-17, un procédé d'obtention de ces composés, ainsi que des produits intermédiaires pour ce procédé. Les nouveaux composés de départ répondent à la formule générale (I) dans laquelle R1 désigne un atome d'H, un groupe alkyle, silyle, acyle, aroyle, alcoxycarbonyle ou alcoxy-alkyle ayant la signification définie de façon plus précise dans la description et, soit a) A désigne un groupe méthylène et R le reste -(CH2)n-CH2-CR2R3OH(n = 1, 2, 3, 4, 5, 6, 7), où R2 et R3 désignent, indépendamment l'un de l'autre, respectivement, un atome d'H, un groupe alkyle C1-4, ou R2 et R3 désignent un cycle cyclopropyl-bis hexyle, soit b) A est une liaison directe et R est un reste carbaldéhyde. Les nouveaux composés sont fabriqués à partir du composé connu (20S)-20-hydroxyméthyl-1, 4-pregnadiène-3-one, par isomérisation en 1,5-diène-3-one puis, dans le cas a) transformation du groupe 20-hydroxyméthyle en un groupe 20-sulfonyloxyméthyle, réduction du groupe 3-céto en groupe hydroxy, formation de la chaîne latérale, oxydation en un composé 7-céto, époxydation en position 1,2, transformation de la 7-cétone en tosylhydrazide correspondant, suivie d'une réduction du 7-tosylhydrazide au moyen d'hydrure de lithium-aluminium. Dans le cas b) le groupe 20-hydroxyméthyle est protegé par un groupe protecteur facilement séparable, puis le 5,7-diène est préparé de façon analogue à la méthode spécifiée sous a), le groupe protecteur est séparé et le composé 20-hydroxyméthyle est oxydé en aldéhyde correspondant.
  [EN] Starting compounds for preparing calcitriol (1$g(a), 25-dihydroxycholecalciferol) and its derivatives showing, as compared with calcitriol, some modifications, particularly in the C-17 lateral chain, a method for preparing these starting compounds and intermediate products for this method are described. The new compounds have the general formula (I), wherein R?1 stands for a hydrogen atom, an alkyl, silyl, acyl, aryl, alkoxycarbonyl or alkoxyalkyl group whose meaning is more closely defined in the description and either a) A stands for a methylene group and R the residue -(CH2?)n?-CH2?-CR?2R?3OH (n = 1, 2, 3, 4, 5, 6, 7), wherein R?2 and R?3 stand independently for a hydrogen atom, a C1-4? alkyl group or R?2 and R?3 stand for a cyclopropyl to cyclohexyl ring or b) A stands for a direct bond and R a carbaldehyde residue. The new compounds are prepared from the known compound (20S)-20-hydroxymethyl-1,1-4-pregnadien-3-one by isomerization to the 1,5-dien-3-one and then, in case a) conversion of the 20-hydroxymethyl group to a 20-sulfonyloxymethyl group, reduction of the 3-keto group to the hydroxy group, construction of the side chain, oxidation to the 7-keto compound, epoxidation in the 1,2 position, conversion of the 7-ketone to the corresponding tosylhydrazide and reduction of the 7-tosylhydrazide with lithium aluminium hydride. In case b), the 20-hydroxymethyl group is protected by a protective group which is readily split off, the 5,7-diene is prepared as in a), the protective group is split off and the 20-hydroxymethyl compound is oxidized to the corresponding aldehyde.
• Umwandlung von (20S)-20-(Hydroxymethyl)pregna-1,4-dien-3-on in (20S)-20-(p-Toluolsulfonyloxymethyl)pregna-1,5-dien-3?-ol und -3?-ol: Zwischenprodukte f�r Vitamin D-Derivate
  作者：S. Wittmann、R. Krieg、R. Prousa、B. Sch�necker、P. Droescher

  DOI：10.1002/prac.19963380145

  日期：——

  Efficient three-step approaches to the two 3-epimeric 22-tosylated 1,5-diene-3,22-diols 6 and 7 starting with (20S)-20-(hydroxymethyl)pregna-1,4-dien-3-one (1) were developed and optimized. Isomerization of 1 to the 1,5-dien-3-one 3 and subsequent tosylation furnished the deconjugated 3-ketone 4. The 3 beta-alcohol 6 was available from 4 by means of in situ generated calcium borohydride. Treatment of 4 with lithium trisiamylborohydride (LS-Selectride) afforded the highest yield of the hitherto unknown 3 alpha-epimer 7. Following the optimized synthesis, 6 and 7 were obtained from 1 in 60% and 50% overall yield, respectively.