CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

II. .33. . SSTRATEGIIESS OFF ENANTIIOMERIIC SSYNTHESSIISS
Before considering in detail the different approaches to asymmetric synthesis, it is
worth looking briefly at all the methods available to obtain chiral compounds in a nonracemic
form.
a) Use of naturally occurring chiral compounds as building blocks. 10
This method actually does not involve any formation of new stereogenic centres,
instead the stereogenic centres are derived from the starting chiral material. Nature
provides a large repertoire of optically active compounds, the so called chiral pool
materials. The most commonly used natural compounds are the amino acids, monoterpenes
and sugars, the latter being most versatile. However, the steroids, alkaloids and
triterpenoids, omnipresent in various plants are hardly of use in such chiral pool synthesis.
This strategy is especially helpful if the desired molecule bears a great resemblance to
cheap enantiopure natural products. Otherwise, a long, tortuous synthesis involving many
steps with attendant losses in yield may be required. At times, it may be difficult to find a
suitable enantiopure starting material; other techniques may prove more fruitful. Also,
utmost care needs to be taken so that there is no chance of racemisation during the reaction
sequence. A well known example 11
of such a synthetic approach is the synthesis of
unnatural amino acids from (S)-serine (6), which is converted to its N-protected analogue
7. Under Mitsonobu conditions, the primary hydroxyl is displaced giving compound 8.
This strained β-lactone undergoes S N 2 ring-opening when treated with a methyl Grignard
reagent in the presence of Cu(I) salts. To complete the synthesis the CBz group is removed
to give the enantiomerically pure product 9 (Scheme I.3.1).
6