7217-07-4Relevant academic research and scientific papers
SYNTHESIS AND CHARACTERISTICS OF ALLYLIC 4-PREGNENE-3,20-DIOLS FOUND IN GONADAL AND BREAST TISSUES
Wiebe, J. P.,Dave, Vinod,Stothers, J. B.
, p. 249 - 260 (1986)
Recently several allylic steroids have been found in gonadal and breast tissues.In order to establish their presence and identity in tissues and determine the possible biological properties, a method for the synthesis of 4-pregnene-3α,20α-diol, 4-pregnene-3α,20β-diol, 4-pregnene-3β,20α-diol, and 4-pregnene-3β,20β-diol was developed using 4-pregnene-3,20-dione (progesterone) as substrate and freshly-prepared aluminum isopropoxide in isopropyl alcohol as reducing agent.The yields were about 19percent, 30percent, 13percent, and 38percent for the 3α,20α-, 3α,20β-, 3β,20α-, and 3β,20β-diols, respectively.The structures and stereochemistry of these diols were established using proton and carbon NMR spectroscopy and infrared and mass spectrometry.
Neurosteroid analogues. 4. The effect of methyl substitution at the C-5 and C-10 positions of neurosteroids on electrophysiological activity at GABA(A) receptors
Han, Mingcheng,Zorumski, Charles F.,Covey, Douglas F.
, p. 4218 - 4232 (2007/10/03)
A series of analogues of the neuroactive steroids 3α-hydroxy-5α- pregnan-20-one and 3α-hydroxy-5β-pregnan-20-one were studied to elucidate the mode of binding of 5α- and 5β-reduced steroids to steroid binding sites on GABA(A) receptors. Analogues which were either 3α-hydroxy-20-ketosteroids or 3α-hydroxysteroid-17β-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17β-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5α- and 5β-reduced steriod modulators of GABA(A) recepters in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABA(A) receptors via interactions at steroid binding sites.
