1β-hydroxytestosterone | 19418-63-4

• 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: 1β-hydroxytestosterone
• 英文别名: 1beta-Hydroxytestosterone；(1R,8S,9S,10R,13S,14S,17S)-1,17-dihydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 19418-63-4
• 化学式: C₁₉H₂₈O₃
• 分子量: 304.43
• InChiKey: LUWKGSHFDJJDAJ-SLMGBJJTSA-N

物化性质

• 沸点：
  478.0±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  睾酮 在 glucose dehydrogenase 、 2,3,4,5,6-pentahydroxy-hexanal 、 Bacillus megaterium P₄₅₀BM₃ enzyme R₁₉ F₈₇A A₁₈₄I T₂₆₀G variant 作用下， 以 aq. phosphate buffer 为溶剂， 反应 16.0h， 生成 1β-hydroxytestosterone
  参考文献：
  名称：

  自然启发性扫描甘氨酸诱变P450BM3（CYP102A1）的类固醇的氧化多样化。

  摘要：

  甾族化合物是处方最广泛的药物，被指定用于治疗各种疾病，包括炎症，心脏病和癌症。功能化类固醇的合成方法对于产生用于药物筛选和开发的类固醇剂很重要。但是，由于类固醇中主要存在惰性的脂肪族CH键，因此化学活化具有挑战性。在这里，我们报道了来自巨大芽孢杆菌的稳定，高活性细菌细胞色素P450酶P450BM3（CYP102A1）的工程设计用于雄烯二酮（AD），脱氢表雄酮（DHEA）和睾丸激素（TST）的单羟基和二羟基化作用。为了设计改变的类固醇结合方向，我们比较了野生型P450BM3与类固醇C19-去甲基化酶CYP19A1的结构，其中AD结合在其活性位点，并鉴定了I螺旋和β4链区域，该区域阻止了P450BM3的这种结合方向。在这两个区域的11个残基上扫描甘氨酸诱变会导致以前未报道过P450BM3的类固醇氧化产物。在第二轮诱变中将这些甘氨酸突变结合在一起，形成了一个小的P450BM3变体文库，该变体能够

  DOI：

  10.1021/acscatal.0c02077

文献信息

• Preparative‐Scale Production of Testosterone Metabolites by Human Liver Cytochrome P450 Enzyme 3A4
  作者：Nico D. Fessner、Matic Srdič、Hansjörg Weber、Christian Schmid、David Schönauer、Ulrich Schwaneberg、Anton Glieder

  DOI：10.1002/adsc.202000251

  日期：2020.7.16

  membrane‐associated human liver cytochrome P450 enzyme (P450) 3A4 in two cycles of a preparative‐scale bioreactor experiment enabled the isolation of the common metabolites 6β‐hydroxytestosterone and 6β‐hydroxyandrostenedione on a 100 mg scale. Side‐product formation caused by enzymes intrinsic to P. pastoris was reduced. In addition more polar testosterone metabolites formed by a P450 3A4‐catalysed bioconversion

  就像药物本身一样，必须评估其代谢产物才能成功开发和批准药物。因此，至关重要的是能够预测药物代谢并合成足够的代谢物量，以进行进一步的药理学测试。这项研究评估了在睾丸激素作为类固醇代表成分的情况下，利用体外生物转化解决这两个挑战的可能性。毕赤酵母细胞的应用在制备规模的生物反应器实验的两个周期中，用表达的膜相关人肝细胞色素P450酶（P450）3A4进行分离，能够以100 mg的规模分离常见的代谢物6β-羟基睾丸激素和6β-羟基雄烯二酮。由巴斯德毕赤酵母固有的酶引起的副产物形成减少了。此外，据报道，由P450 3A4催化的生物转化形成的极性睾丸激素代谢物比已知的单羟基化代谢物多，并且6-脱氢-15β-羟基睾丸激素以及二羟基化类固醇6β，16β-二羟基睾丸激素，6β，17β分离并通过NMR分析验证了-dihydroxy-4-androstene-3,16-dione和6β，12β-dihydrox
• METHOD FOR BIOCATALYSIS USING FILAMENTOUS FUNGI
  申请人：Reese Paul B.

  公开号：US20090246850A1

  公开（公告）日：2009-10-01

  A method is disclosed in which filamentous fungi are macerated and encapsulated in an inert matrix to form beads, which can be used to promote reactions carried out by the fungi. The beads are useful, e.g., for producing compounds and compound libraries.

  本发明公开了一种方法，其中纤维状真菌被磨碎并封装在惰性基质中形成珠子，可用于促进真菌所进行的反应。这些珠子可用于生产化合物和化合物库等领域。
• Method for biocatalysis using filamentous fungi
  申请人：The University of the West Indies

  公开号：EP2093285A1

  公开（公告）日：2009-08-26

  A method is disclosed in which filamentous fungi are macerated and encapsulated in an inert matrix to form beads, which can be used to promote reactions carried out by the fungi. The beads are useful, e.g., for producing compounds and compound libraries

  本发明公开了一种方法，将丝状真菌浸渍并封装在惰性基质中形成珠子，珠子可用于促进真菌进行的反应。这些珠子可用于生产化合物和化合物库等。
• STABLE-ISOTOPE-LABELED COMPOUND
  申请人：ASKA Pharmaceutical Co., Ltd.

  公开号：EP3725795A1

  公开（公告）日：2020-10-21

  The invention provides a novel internal standard useful in the measurement of androgens, a method capable of measuring the androgen in a highly selective and highly sensitive (accurate) manner using liquid chromatography mass spectrometry with simplified pretreatments, and a method for diagnosis of a disease using the androgen measurement method. The novel stable isotope-labeled compound is synthesized by performing reduction reaction in a specific solvent. An androgen is measured using this novel stable isotope-labeled compound as an IS.

  本发明提供了一种可用于测量雄激素的新型内标物，一种可利用液相色谱质谱法以高选择性和高灵敏度（精确）的方式测量雄激素并简化预处理的方法，以及一种利用雄激素测量方法诊断疾病的方法。 新型稳定同位素标记化合物是在特定溶剂中通过还原反应合成的。使用这种新型稳定同位素标记化合物作为 IS 测量雄激素。
• Immunoaffinity purification of aromatase cytochrome P-450 from human placental microsomes, metabolic switching from aromatization to 1β and 2β-monohydroxylation, and recognition of aromatase isozymes
  作者：Yoshio Osawa、Nobutake Yoshida、Mary Fronckowiak、Jo Kitawaki

  DOI：10.1016/0039-128x(83)90058-2

  日期：1987.7

  Microsomal estrogen synthetase (aromatase) cytochrome P-450 was purified from fresh human placental microsomes by monoclonal anti-aromatase P-450 antibody-Sepharose 4B chromatography. The purified P-450 showed a single band of 55 kDa on SDS-polyacrylamide gel electrophoresis and the aromatase specific activity on reconstitution was 70 nmol/min/mg protein. The purified P-450 was stable with a t 1/2 of approximately 2 years on storage at -90 degrees C and showed Km = 43 nM for androstenedione aromatization. However, it was unstable under spectral measurement conditions in the presence of sodium dithionite and carbon monoxide and the carbon monoxide difference spectra showed a maximum at 450 nm and a specific content of 9.1 nmol of P-450/mg protein, giving a turnover number of approximately 7.7 per min for the purified aromatase. The one-step immunochemical purification method gave a 490-fold increase of specific activity with 55% yield of aromatase activity of the original microsomes. Analysis of androgen metabolism by the purified aromatase and an apparent large kinetic isotope effect found at the secondary positions when using [19(-3)H3, 4(-14)C] androgens revealed metabolic switching from the first 19-hydroxylation to 1 beta- and 2 beta- monohydroxylation by aromatase. Substrate specificity for [19(-3)H3]androstenedione and testosterone was indicated by differences in the extent of metabolic switching (18% and 30%) and in the 2 beta/1 beta ratio (60/40 and 10/90, respectively). The mouse monoclonal antibody used for immunoaffinity purification suppresses aromatase activity of human placenta, but was totally ineffective for aromatase in goldfish brain and rat ovary. Rabbit polyclonal antibodies to human placental aromatase P-450 suppressed both human placental and rat ovarian aromatase but were ineffective for goldfish brain aromatase. The study indicates that they are isozymes of aromatase based on different structures of P-450.