Lecture 1:

Kinetic resoltuion:

50 : 50 of R : S -> slow and fast reaction rate and realted rate constants
(different as possible)
Theoreticallly no substarte left

FAST DIVIVED BY SLOW!e.e. (enantiometric excess)

e.e. of substrae = S - R / S + R (more of S since slower)
product = P - Q / Q + P (more of P since faster)

Kinetic resolution: two enantiomers react with different reaction scan rates with a
chrial catalys or ragent -> results is an enantioenriched samples of the less
reactive enantiomer

ee of the unreacted material

Asymmetric sythesis:

when you have NOT chiral substrate and you create chrial producte -> one enantiomer
will be faster than the other one

Chirality:

= if it CANNOT be superposed on its mirror image by any combination, rotation,

translation etc

chiral molecule = (exists in two steroisomers) -> mirror images = enantiomers

= RIGHT AND LEFT = can be mirrored but NOT superimposed
= enantiomers are mirror images of each other, so also stereoisomer

Sterioisomer = iosmer that differ in the 3D arrangement of atoms

enantiomers = sterioisomers that are not-superimposable mirror immages

Chiral atom should be bound to 4 different atoms (USUALLY) = chiral center

(tetrahedral carbon) that has 4 different groups

Lecture 2:

Fine chemicals -> complicated mlecule with defined purity and interedted to prudce
with enzyme

Lecture 3:

Kinetic resolution (resolution = seperates two enenatiomers for racemic mixture):

- is kinetically controlled -> if you wait to long you will reach equlibium and you
wont get ee (so for faster reaction rate, reaches quicker eqilibirum and at some
point also lower recation rate -> bcs emnantiomers, so no phyical different
and therefore "same" equilibirum and therefore NO ee and therefore reaches at
some point zero!
THEREFORE: if interesyed in enenatiomer excess -> reaction needs to be stopped
before reaching equilibrium
- kinetic bcs two reaction rates
- start with 50:50 conc of chrial compund in racemic form
- chrical catalyst (e.g. enzyme)
- catalyst will react with one substrate/chiral compounds more prefered to generate
product
- then: fast-reacting substrate has been consumde, only 50% of original is left and
50% converted
--> then entationmers 50:50 seperated in product and unreacted substarte
= different compounds!

the bigger the difference between the reaction rates, the bigger the difference
between enantiomer relationship

E = entioselectivity = ratio between the fast reaction rate constant divided by the
slow reaction rate constant, e.g. 5 = faster reaction is five times higher than
slower reaction rate

E > 100 -> infinite

ee substrate = S (slow) - R (fast) / S + R -> depending

on rate constant, steeper increase of graph, because substrate gets quicker
converted, one substarte is rather preferred to be used up than other one, that's
why when
rate is
up, starting from 100

ee product = P (fast) - Q (slow) / P + Q (excess of P compared to Q) -> depedning

on rate constant, higher starting point off eep, quicker generation of P when
higher rate, since more produced compared to slower rate constant
also
reaches quicker 50:50 conversion relationship

E = kR / kS

lower when equilibrium (reversible), top when no equilibrium (irreversible)

Euqations: c = conversion
experimental values needed (specific x and y) to use
K = equilibrium constant

How to calculate E value?

LOWER THAN 30% conversion when lines are still combined otherwise seperated ->
valid only for top line!

"bigger" equation -> if you do not have conversion

reversible reaction -> ee drops and lower ee at a certian point of reaction ->
displace equilibrium towards and reversible reaction

push chemical reaction towards the product side -> excess of cosubstare & remove of
product & activated esters (reaction would not go in reverse side)

change pH = changes enzyme

over 100 E values = kinetic reslution process is useful (otherwise you need to
improve it)

Kinetic resolution = max. yield are only 50% either way because racemat solution
(not really sustainable!)

Entropy and enthalpy:

# = transition state

Racemic temperatrue:

where cross the zero line = racemic temperature

Two-setp resolution process:

stop reaction (step1) before it will drop too much and isoltae product (enough ee)
but reaction only 40% run and remove product

continoue to run with same substrate until convresion to 60% and then isolate
substarte at 60% and remaining 40% is isolate

Sequential process:

substrate passes the active site twice -> actually obvserve higher
eneatioselectivity than each of the steps
only possible for substarte with two active groups

use enzyme twice on the same substrate-> symmetry + stereoselectivty -> enzyme has
preference for one of the enatiomers (ester hydrolysis and ester sythesis) -> will
reinforce the ee

Decracemization:

= transformation of a racemate into a single steroisomeric product in 100%

theoretical yield

1) Dynamic kinetic resolution:

slow and fast reaction rate transformed /enenatiomer switched -> as lomg as top
reaction fast, it will be refilled from sloewr substarte -> in theory: 100% product
yield
challenge: transform one enantiomer in another enantiomer (that it can react)

2) enantioconvergent processes:
one enantiotnmer is fast and other enantiomer is turinng it into the same product =
inversion ( can be done with two enzymes)

3) Cyclic deracemization:
a and b racemats, 2 enzmyes, produce the same prodcyt and then taking it back to
the same substrate