BPS319 PBL 3 Natural Product Chemistry vs Kinetic Isotope Effects Coursework | University of Liverpool

BPS319 PBL 3 Coursework

In this module, we studied the Woodward synthesis of cholesterol, which consists of 35 linear steps. Since the 1950’s when this total synthesis route was published, there has been much interest in the development of improved synthetic routes towards steroid compounds.

The diketone molecule shown below, represents a key intermediate in the total synthesis of numerous biologically relevant natural products, including steroids.

a) Draw a reaction mechanism to show the formation of the key intermediate shown, from 2-methyl-1,3-cyclohexanedione and 3-buten-2-one under basic conditions. (7 marks)

The above reaction results in the formation of a new stereogenic centre. An asymmetric synthesis which uses L-Proline as an organocatalyst affords the stereoisomer shown below in 76% ee.

b) Using the Cahn-Ingold-Prelog rules, assign the stereochemistry of the enantiomer shown. Show your full working by drawing an annotated structure. (1 mark)

c) Given that the enantiomeric excess is 76% in favour of the enantiomer drawn, what is the relative proportion of each enantiomer? Show your full working. (2 marks)

d) With full justification identify the rate determining step (RDS) within your Robinson Annulation mechanism, highlighting it in your mechanism from part a. (4 marks)

e) Design and draw an isotopically labelled reactant that could corroborate your choice of RDS. (2 marks)

f) What type of Kinetic Isotope Effect and relative reaction rate would be seen for your labelled substrate if your choice of RDS is correct? Justify your answer. (4 marks)