“…A comparison with the data from 6 shows that the Schering compound, probably necessitated through unfavorable steric repulsions of the 17β- and 11β-substituents in the chair conformation of the C-ring, takes on a C-ring twist-boat conformation that forces the D-ring to assume a 16β,17α-half-chair conformation. In addition, molecular mechanics calculations support a twist-boat C-ring conformation for 11β-unsubstituted compounds . If one again takes the 13α,14β-half-chair conformation of the D-ring as the starting point, pseudorotation in the same direction as for 6 results in an angle for the Schering compound of Δ = 504° (for rotation in the opposite direction Δ = −216°).…”
Section: Resultsmentioning
confidence: 90%
“…In addition, molecular mechanics calculations support a twist-boat C-ring conformation for 11β-unsubstituted compounds. 15 If one again takes the 13R,14β-half-chair conformation of the D-ring as the starting point, pseudorotation in the same direction as for 6 results in an angle for the Schering compound of ∆ ) 504°(for rotation in the opposite direction ∆ ) -216°).…”
The diastereomeric 16-bromo- and 16-azido-17-alcohols 5-8, 11, 12, 16, and 17 and 17-ketones 3, 4, 9, and 10 of the 13alpha-estra-1,3, 5(10)-triene series were synthesized as precursors for biologically active compounds and chiral ligands for metal complexation. Conformational investigations of these and some other compounds via X-ray analysis and (1)H NMR spectroscopy show the existence of compounds with the classical steroid conformation (ring C chair, restricted conformation of ring D) and such with an atypical ring C twist-boat and a flexible ring D conformation. It could be shown that 17beta-substituents or flattening of the D-ring are responsible for the twist-boat conformation, whereas compounds containing a 17alpha-substituent or 17-keto group possess the classical conformation. By varying the substituents, compounds with either of these conformations can be intentionally synthesized. MO calculations confirmed the relative stability of the twist-boat conformation.
“…A comparison with the data from 6 shows that the Schering compound, probably necessitated through unfavorable steric repulsions of the 17β- and 11β-substituents in the chair conformation of the C-ring, takes on a C-ring twist-boat conformation that forces the D-ring to assume a 16β,17α-half-chair conformation. In addition, molecular mechanics calculations support a twist-boat C-ring conformation for 11β-unsubstituted compounds . If one again takes the 13α,14β-half-chair conformation of the D-ring as the starting point, pseudorotation in the same direction as for 6 results in an angle for the Schering compound of Δ = 504° (for rotation in the opposite direction Δ = −216°).…”
Section: Resultsmentioning
confidence: 90%
“…In addition, molecular mechanics calculations support a twist-boat C-ring conformation for 11β-unsubstituted compounds. 15 If one again takes the 13R,14β-half-chair conformation of the D-ring as the starting point, pseudorotation in the same direction as for 6 results in an angle for the Schering compound of ∆ ) 504°(for rotation in the opposite direction ∆ ) -216°).…”
The diastereomeric 16-bromo- and 16-azido-17-alcohols 5-8, 11, 12, 16, and 17 and 17-ketones 3, 4, 9, and 10 of the 13alpha-estra-1,3, 5(10)-triene series were synthesized as precursors for biologically active compounds and chiral ligands for metal complexation. Conformational investigations of these and some other compounds via X-ray analysis and (1)H NMR spectroscopy show the existence of compounds with the classical steroid conformation (ring C chair, restricted conformation of ring D) and such with an atypical ring C twist-boat and a flexible ring D conformation. It could be shown that 17beta-substituents or flattening of the D-ring are responsible for the twist-boat conformation, whereas compounds containing a 17alpha-substituent or 17-keto group possess the classical conformation. By varying the substituents, compounds with either of these conformations can be intentionally synthesized. MO calculations confirmed the relative stability of the twist-boat conformation.
“…These two basic ring conformations have been found previously in the case of 13a steroids. [33] An average structure from the simulation for each basic C-ring conformation as well as some representative dynamics snapshots were selected; the conformation within the 17-side chain was then adopted so as to allow H abstraction, and these structures were finally energy-minimized once more. The conformations of five-and six-membered rings were judged by using asymmetry parameters DC s and DC 2 [34] and phase angles of pseudorotation D. [35] To model the binuclear complex with the four-membered ring containing copper and oxygen, the crystal structure of bis[aqua-(m 2 -hydroxo)-(2,2'-bipyrimidinyl-N,N')-copper] dinitrate tetrahydrate (CSD refcode: [36] PEMPEC) was selected.…”
Copper(I) complexes incorporating the isomeric bidentate ligands IMPY (iminomethyl-2-pyridines) or AMPY (aminomethylene-2-pyridines) are quite unusual in their ability to bind and activate molecular oxygen. Using these complexes, hydroxylations of nonactivated CH, CH2, or CH3 groups in the gamma-position in relation to the imino-nitrogen atom, and with a specific orientation of one H atom with respect to the binuclear Cu-O species, can be achieved in synthetically useful yields. Through mechanistic studies employing conformationally well-defined molecules (for example, cyclic isoprenoids), coupled with solid-state X-ray structure analyses and force-field calculations, we postulate a seven-membered transition state for this reaction in which six atoms lie approximately in a plane. This plane is defined by the positions of the lone pairs on the nitrogen atoms, as well as the copper and the oxygen atoms. For a successful hydroxylation, one hydrogen atom should be located close to this plane. Prediction of the stereochemical course of these reactions is possible based on a simple geometrical criterion. The convenient introduction of IMPY and AMPY groups as auxiliaries into oxo and primary amino compounds and the simple hydrolysis after the hydroxylation procedure has allowed the synthesis of 3-hydroxy-1-oxo and 3-hydroxy-1-amino compounds. If desired, the 3-hydroxy-1-IMPY and -1-AMPY compounds can be reduced with NaBH4 to obtain 3-hydroxy-1-aminomethylpyridines. For a successful hydroxylation procedure, the method employed for the synthesis of the CuI complexes is very important. Starting either from CuI salts or from CuII salts with a subsequent reduction with benzoin/triethylamine may turn out to be the better way, depending on the ligand and the molecular structure.
“…Progesterone antagonists can be used to terminate pregnancy by menses induction: further details and structure−activity patterns for progesterone derivatives have been reported by Bohl and by Bursi and Groen . The 3D query structure for the antiprogestational steroid was taken from the CSD crystal structure SESJUV and is shown in Figure . 3 Query structure for antiprogestational steroid together with CCP representation (hydrogens in query not shown).…”
Crystal structures taken from the Cambridge Structural Database were used to build a ring scaffold database containing 19 050 3D structures, with each such scaffold then being used to generate a centroid connecting path (CCP) representation. The CCP is a novel object that connects ring centroids, ring linker atoms, and other important points on the connection path between ring centroids. Unsupervised searching in the scaffold and CCP data sets was carried out using the atom-based LAMDA and RigFit search methods and the field-based similarity search method. The performance of these methods was tested with three different ring scaffold queries. These searches demonstrated that unsupervised 3D scaffold searching methods can find not only the types of ring systems that might be retrieved in carefully defined pharmacophore searches (supervised approach) but also additional, structurally diverse ring systems that could form the starting point for lead discovery programs or other scaffold-hopping applications. Not only are the methods effective but some are sufficiently rapid to permit scaffold searching in large chemical databases on a routine basis.
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