Exercise 4. Conformational Analysis using Crystal Structures.

The Cambridge Structure Search and Retrieval Database contains the coordinates of essentially all the crystallographic information on small molecules available in the chemical literature. It can be accessed from any academic site in the UK and both numeric and graphical information is available.

For this part of the Practical we need to learn how to obtain a line to the UK Chemical Database Service at Daresbury - use the ID and Password obtained from Dr. Harrison, and respond to the prompt as follows :

%quest mysearch (a filename choosen by you for identification)
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>TERM XR4 (X-windows terminal type)
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>DEVI MOUSE
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>MENU
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This provides a window in which the molecule can be drawn, and other information added to the search. To keep it simple, here are the basic instructions :

Molecules are drawn by defining atoms with the cross-hair which is activated by a mouse click. Try drawing a cyclohexane ring freehand. Any mistakes can be rectified with the delete atom and delete bond commands, which you might need to use regularly at the beginning! Simple atom and bond replacements may be made by activating the appropriate item in the "palette" - check that you can make a bond to oxygen internal and external to the ring. At this stage you are ready to progress to studying the conformations of decalins by viewing their crystal structures, and the molecules you need to draw are shown below. There are two separate projects, one which identifies conformations accessible to 1-decalones and the other the conformations of 2-decalol derivatives. The reason that the search molecules are defined by adding hydrogens is that it avoids the inclusion of steroid and terpene nuclei which will inevitably provide several dozen extra "hits" not relevant to the problem, so you will need to adhere to these quite carefully. If you have time, or if you are working as a pair, do both searches - but one will suffice for an individual mark-off.

The first search "substructure" will find all derivatives of decalin which are unsubstituted or have substituents only at the 2-position. When you have completed the drawing :

click on define structure

click on fast quest

This will prompt the scrolling of the database until relevant structures are encountered. From Search Molecule 1 there should be two such hits. The first time this occurs, set the prompt "to 2D" in the top right hand corner and check whether the compound is significant to your search. If it is then change the format with the prompt "to 3D" and examine the structure model. There are rotation, translation and sizing tools - practice manipulating the structure. The questions you will need to answer are :

What is the stereochemistry of the molecule as revealed by X-ray? - make an accurate 3D drawing which relects this
Are there any notable conformational features in the structure?
How do the results compare with your molecular modelling by CAChe?

When you are satisfied that you have extracted all the necessary information, press "reject" and scrolling continues until the next hit. In addition, reject any structure which is not a simple bicyclic compound. The searches have been designed to limit these extraneous possibilities, but there will still be several in each series.

If you have done the searches correctly, there will be two structures in each series. From search structure 1, these will be stereoisomers of O-substituted 2-decalols. For the search structure 2 they will be diketones, and the conformational analysis gives a striking result.