3beta,16beta-Diacetoxyandrost-5-en-17-one | 10587-75-4

• 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: 3beta,16beta-Diacetoxyandrost-5-en-17-one
• 英文别名: 17-oxoandrost-5-en-3β,16β-diyl diacetate；17-oxoandrost-5-en-3β,16β-yl diacetate；3β,16β-diacetoxyandrostan-5-en-17-one；3β,16β-diacetoxyandrost-5-en-17-one；3β,16β-diacetoxy-androst-5-en-17-one；3β,16β-Diacetoxy-androst-5-en-17-on；Androst-5-en-17-one, 3,16-bis(acetyloxy)-, (3beta,16beta)-；[(3S,8R,9S,10R,13S,14S,16S)-16-acetyloxy-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] acetate
• CAS: 10587-75-4；16597-57-2
• 化学式: C₂₃H₃₂O₅
• 分子量: 388.504
• InChiKey: RWUHRLQWZKUBTF-HVWUICSASA-N

物化性质

• 熔点：
  180-181 °C
• 沸点：
  482.6±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3beta,16beta-Diacetoxyandrost-5-en-17-one 在 palladium on activated charcoal 吡啶 、 盐酸 、 氢气 、 乙酸酐 、 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 甲苯 为溶剂， 反应 0.5h， 生成 3β-acetoxy-16α-hydroxy-23,24-dinor-5α,17βH-cholan-22-oic acid-lactone
  参考文献：
  名称：

  Mechanistic studies of the rearrangements of steroidal 16,17-ketols and syntheses of 20→16-cis-γ-carbolactones

  摘要：

  Utilization of 17-keto-androstanes as starting materials for the synthesis of alpha- or beta-oriented steroidal 20-->16-gamma-carbolactones has been explored following two different strategies. A highly efficient, stereospecific protocol has been developed for the beta-oriented cis-gamma-lactone. A different approach, involving prior attachment of a 3-carbon side chain on C-17 of a 17-oxo-16 beta-acetoxyandrostane led to the epimeric, cc-oriented lactone. The mechanism of the rearrangement of epimeric 16 beta- or 16 alpha-hydroxy-17-ketoandrostanes to 17 beta-hydroxy-16-keto-androstanes was studied by C-13 NMR spectroscopy. The former occurs through a 1,2-sigmatropic H-shift, while the latter is likely to take place by simple enolization-reprotonation. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00042-5
• 作为产物：
  描述：

  3β-acetoxy-5α,6β-dichloro-androsta-17-one 在 lead(IV) acetate 、 硫酸 、 溶剂黄146 、 锌 作用下， 以 溶剂黄146 为溶剂， 生成 3beta,16beta-Diacetoxyandrost-5-en-17-one
  参考文献：
  名称：

  16氧化ANDROST-5-EN-3-BETA-OL衍生物的合成。

  摘要：

  约有16种含氧的雄甾-5-烯类固醇，它们均为类固醇代谢物，是通过3β-乙酰氧基-5α, 6β-二氯雄甾烷-17-酮制备的。

  DOI：

  10.1248/cpb.12.808

文献信息

• Synthesis of 3β,16β,19-trihydroxyandrost -5-en-17-one and 16β3,19-dihydroxyandrost-4-ene-3,17-dione and their 19-oxo derivatives
  作者：Numazawa Mitsuteru、Mutsumi Ayako、Hoshi Kumiko、Ishimura Shigechika、Shoji Satomi、Sekihara Hisahiko

  DOI：10.1016/0039-128x(90)90095-s

  日期：1990.9

  Abstract 3β,l6β,l9-Trihydroxyandrost-5-en-17-one (12) was synthesized from 5α-bromo-3β-acetoxy-6β,19-ep-oxyandrostan -17-one ( 2 ) through acetoxylation at C-16β of the enol acetate 4 with lead tetraacetate and reductive cleavage of the epoxide ring with une dust yielding the 3β,I6β-diacetoxy-19-hydroxy steroid 11 , followed by hydrolysis of the acetoxy groups with sulfuric acid. Jones oxidation of

  摘要 3β,l6β,l9-Trihydroxyandrost-5-en-17-one (12) 由 5α-bromo-3β-acetoxy-6β,19-ep-oxyandrostan -17-one ( 2 ) 通过 C-16β 的乙酰氧基化合成烯醇乙酸酯 4 与四乙酸铅和环氧化物环与 une 粉尘的还原裂解产生 3β,I6β-二乙酰氧基-19-羟基类固醇 11，然后用硫酸水解乙酰氧基。化合物 11 的琼斯氧化，然后酸水解得到 19-氧代甾体 15。5α-Bromo-3β-hydroxy-16β-acetoxy-6β, 19-epoxyandrostan-17-one ( 8 )，通过用氢氧化铵选择性水解 3-甲酸酯 5 获得，用琼斯试剂氧化得到 3-oxo类固醇 16，通过锌粉处理转化为 19-羟基衍生物 17。16β,19-Dihydroxyandrost-4-ene-3, 17-二酮
• Production of 16β-(acetoxy)acetoxy derivatives by reaction of 17-keto steroid enol acetates with lead (IV) acetate
  作者：M Numazawa

  DOI：10.1016/s0039-128x(01)00103-9

  日期：2001.10

  16beta-acetoxy-17-ketones with the lead reagent did not yield the corresponding (acetoxy)acetates. Reaction of the enol acetate 3 with Pb(OCOCD(3))(4) in CD(3)COOD yielded principally the labeled (acetoxy)acetate 10-d(3), which had a CD(3)COOCH(2)COO moiety at C-16beta. In contrast, when the deuterated enol acetate 3-d(3), which was obtained by treatment of the 17-ketone 14 with (CD(3)CO)(2)O in the presence

  用 Pb(OCOCH(3))(4) 处理 3beta-acetoxyandrost-5-en-17-one 及其 5alpha-reduced 类似物 5alpha-androstan-17-one 和醋酸雌酮，1-4 的烯醇乙酸酯在乙酸和乙酸酐中得到先前未报道的产物 16β-（乙酰氧基）乙酰氧基-17-酮 8-10 和 12，产率 9-15%，以及已知的主要产物 16β-乙酰氧基-17-酮 5- 7 和 11。用先导试剂对 16β-乙酰氧基-17-酮进行类似处理没有产生相应的（乙酰氧基）乙酸盐。烯醇乙酸酯 3 与 Pb(OCOCD(3))(4) 在 CD(3)COOD 中的反应主要产生标记的（乙酰氧基）乙酸酯 10-d(3)，其具有 CD(3)COOCH(2)COO C-16beta 的部分。相反，当氘代烯醇乙酸酯 3-d(3) 时，通过在 LDA 存在下用 (CD(3)CO)(2)O 处理
• Lipase-Catalysed Regioselective Deacetylation of androstane derivatives
  作者：Alicia Baldessari、Andrea C. Bruttomesso、Eduardo G. Gros

  DOI：10.1002/hlca.19960790408

  日期：1996.6.26

  series of acetoxy derivatives of androstane was deacetylated in organic solvents by several lipases. The most satisfactory results were obtained with lipase from Candida cylindracea (CCL) and Candida antarctica (CAL). In some derivatives, CCL and CAL showed an overwhelming regioselectivity towards the removal of the 3β- or the 17β-acetyl group (see Table 2). Three new steroid derivatives were obtained

  在多种有机溶剂中，几种脂肪酶使雄烷烷酮的一系列乙酰氧基衍生物脱乙酰化。用来自假丝酵母（CCL）和南极假丝酵母（CAL）的脂肪酶获得了最满意的结果。在某些衍生物中，CCL和CAL对除去3β-或17β-乙酰基表现出压倒性的区域选择性（参见表2）。通过这种方法获得了三种新的类固醇衍生物。给出了这些酶的行为的假设原理。
• Preparation of 3β,16β-dihydroxyandrost-5-en-17-one: Stabilization of its α-ketolic group toward alkali by formation of a semicarbazone
  作者：Vernon R. Mattox、Albert N. Nelson

  DOI：10.1016/0039-128x(76)90143-4

  日期：1976.6

  Abstract Alkaline hydrolysis of a 16β-acetoxy-17-oxo steroid is accompanied by almost complete rearrangement of the product to a 16-oxo-17β-hydroxy steroid. Hydrolysis can be achieved without rearrangement by 1) formation of a C-17 semicarbazone, 2) alkaline removal of the acetate group, and 3) removal of the semicarbazone group in the presence of pyruvic acid-acetic acid. By employing this technique

  摘要 16β-乙酰氧基-17-氧代类固醇的碱性水解伴随着产物几乎完全重排为16-氧代-17β-羟基类固醇。水解可以在不重排的情况下通过 1) 形成 C-17 缩氨基脲，2) 碱去除乙酸酯基团，和 3) 在丙酮酸-乙酸存在下去除缩氨基脲基团而实现。通过使用该技术，从其二乙酸盐以65%的产率获得标题化合物。
• C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists
  作者：Padma Marwah、Ashok Marwah、Henry A. Lardy、Hiroshi Miyamoto、Chawnshang Chang

  DOI：10.1016/j.bmc.2006.05.022

  日期：2006.9

  Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C-19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3 beta,17 beta-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3 beta-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3 beta-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer. (c) 2006 Elsevier Ltd. All rights reserved.