Related Experiment Video
Updated: Jul 2, 2026
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
05:15
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
5alpha-Androst-3-en-17-one oxime.
L C R Andrade1, M J M de Almeida, F M Fernandes Roleira
1CEMDRX, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, P-3004-516 Coimbra, Portugal. lourdes@pollux.fis.uc.pt
Acta Crystallographica. Section C, Crystal Structure Communications
|September 2, 2008
Summary
A C17-oxime derivative, a potent aromatase inhibitor, surprisingly showed no inhibitory power. Crystal structure analysis revealed hydrogen bonds correlating to this loss of function.
Area of Science:
- Medicinal Chemistry
- Structural Biology
- Crystallography
Background:
- Aromatase inhibitors are crucial in treating hormone-dependent cancers.
- C17-oxime derivatives are known potent aromatase inhibitors.
- The title compound, a C17-oxime derivative, was investigated for its inhibitory potential.
Purpose of the Study:
- To investigate the structural basis for the unexpected lack of aromatase inhibitory activity of a C17-oxime derivative.
- To elucidate the role of intermolecular interactions in the compound's biological function.
Main Methods:
- Single crystal X-ray diffraction was employed to determine the crystal structure.
- Analysis of hydrogen bonding networks (C=N-O-H...N and C-H...O) within the crystal lattice.
- Correlation of observed structural features with the compound's biological activity.
Main Results:
- The compound crystallizes with two independent molecules in the asymmetric unit.
- A distinct hydrogen-bonding scheme involving C=N-O-H...N dimers and C-H...O interactions was identified.
- These hydrogen bonds contribute to the overall crystal cohesion.
Conclusions:
- The observed hydrogen-bonding network in the crystal structure is strongly correlated with the compound's lack of aromatase inhibitory power.
- Structural factors, specifically intermolecular hydrogen bonding, can significantly impact the biological activity of potential drug candidates.
- This study highlights the importance of structural analysis in understanding drug mechanism and design.
Related Concept Videos
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
02:38Structure and Nomenclature of Epoxides
Cyclic ethers are heterocyclic compounds with an oxygen atom in the ring along with carbon atoms. They are named depending on the number of carbon atoms present in their ring system. Cyclic ethers with a three-membered ring system are called “oxirane”, four-membered ring systems as “oxetane”, five-membered ring systems as “oxolane”, and six-membered ring systems as “oxane”. The cyclic structure of these rings imposes angle strain, and this strain is more in the ring having a smaller number of...
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
02:36Oxymercuration-Reduction of Alkenes
Oxymercuration–reduction of alkenes is one of the major reactions converting alkenes to alcohols. It involves the hydration of alkenes with mercuric acetate in a mixture of tetrahydrofuran and water, forming an organomercury adduct. This is followed by a demercuration step in which the adduct is reduced to an alcohol using sodium borohydride.
01:19Nitrosation of Enols
The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.