4. Studies have shown that one stereoisomeric forms of compound E is an effective agent
against certain types of neurodegenerative disorders. Recognize that structure E
contains a decalin type system, as illustrated in structure F, and that the nitrogen can
be treated just like a carbon.
8a
ΝΗ
HO
NH
6
3
P
HO
4a
CO2H
E
F
a) Use your model kits to analyze the ring juncture. Make models of the cis as well as
the trans ring juncture of structure F. You should have four different models. Identify
the stereochemical relation between them as diastereomeric or enantiomeric. Draw
the isomers and assign the R and S configuration to the stereocenters at the ring
fusion.
b) Although the trans ring juncture is the energetically more favorable one, the
compound with cis ring juncture is the stereoisomer of structure E that shows
biological activity. Make models of structure E that have the cis ring juncture
exclusively. Set the stereochemistry of C3 as shown in structure E and vary the center
at C6 in relation to that at C3. Again, there are four different models. Draw them and
convince yourselves that none of them are enantiomers by assigning the R or S
configuration to all four of the stereocenters in each of the compounds.
c) The stereoisomer of compound E that shows the greatest biological activity has a cis
ring fusion with substituents at C3 and C6 that are both equatorial. Which of the
stereoisomers that you drew encompasses these constrains? Identify it by recording
the absolute configuration at C3, C4a, C6, and C8a.