Download Bio-Organic Mechanism Game – Simplistic biochemical structures

1
Bio-Organic Mechanism Game – Simplistic biochemical structures and simplistic organic
reaction mechanisms are used to explain common biochemical transformations. Simplified
biochemical molecules are presented first.
Many biomolecules have a somewhat complex structure that makes it difficult to write out step by
step mechanisms. However, if we simplify those structures to the essential parts necessary to
explain the mechanistic chemistry of each step, it becomes much easier to consider each step
through an important cycle. I have proposed possible simplified structures that are used in the later
examples of biochem cycles and problems. The usual strategy in biochem cycles is to just write
names, or perhaps, names and a structure. Occasionally a few mechanistic steps are suggested, but
almost never is a detailed sequence of mechanistic steps provided. Since it is hard to find such
detailed mechanistic steps anywhere (sometimes they are not known) our proposed steps are, of
necessity, somewhat speculative. In this book we are not looking for perfection, which is not
possible, but for sound organic logic that is consistent with the biochemical examples presented
below. There is great satisfaction in blending organic knowledge with real life reactions that help
explain how life works. In working through some of the problems, you may develop an alternative
mechanism that is just as good, or even better than the one I have proposed. If you do, I hope you
will share it with me and if an improved version of this book ever gets written I can include it the
next edition (and give you credit). It is almost certain that I have made some errors and I would
appreciate it if you would let me know about them.
Biomolecules and our simplified representation.
1. ATP – adenosine triphosphate – phosphorylation, energy source
NH2
N
O
O
P
O
O
ATP
O
=
O
P
O
O
O
P
O
O
simplified structure
N
O
P
O
CH2
O
H
H
OH
H
OH
H
actual structure
N
O
N
2. NAD+ and NADP+ - nicotinamide adenine dinucleotide (hydride acceptor)
NH2
CONH2
N
=
N
R
N
H 2C
P
O
P
O
CH2
OH HO
O
O
simplified
structure
O
actual
structure
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
N
O
O
O
N
O
N
H
H
OH
H
OH NADP+ has a
H
phosphate here.
2
3. NADH and NADHP - nicotinamide adenine dinucleotide (hydride donor)
H
H
H
NH2
CONH2
H
N
O
=
N
H2C
N
OH HO
R
O
O
P
N
O
O
O
P
O
CH2
O
N
O
H
H
OH
H
OH
H
simplified
structure
N
NADPH has a
phosphate here.
4. Vitamin B-6 – pyridoxal phosphate (amino acid metabolism, transamination with -ketoacids,
decarboxylation, removal of some amino acid side chains, epimerizations)
1o amine version of Vit B-6
NH2
aldehyde version of Vit B-6
NH2
H
H
O
-2
O3PO
O
H
simplified
structure
O
H
interconvert
via imine,
tautomers,
hydrolysis
O
-2
O3PO
=
N
H
=
N
N
H
H
H
actual
structure
simplified
structure
actual
structure
N
5. TPP – Thiamine diphosphate (decarboxylation and enamine chemistry with proton or
carbohydrates)
N
N
B
N
simplified
structure
N
=
H
S
N
R
R
NH2
ylid form
of TPP
S
O
P
O
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
H
O
O
S
O
P
O
O
CH2
actual
structure
3
6. Coenzyme A (acyl transfer)
All of this is "Co-A"
O
O
O
S
O
N
H
H
P
N
H
O
O
P
O
N
O
O
N
OH
Thiol esters form here.
H
NH2
O
O
N
N
HO
OH
CoA
S
CoA
This is an
acetyl group
simplified
structure of CoA
S
actual
structure
simplified structure
of acetyl Co-A
7. FAD / FADH2 – Flavin adenine dinucleotide (oxidation – reduction) – used to deliver hydride to
C=C or take hydride from CH-CH (fatty acid metabolism, etc.)
O
O
P
O
O
P
O
N
NH2
O
O
O
N
HO
OH
N
actual structure
N
HO
OH
OH
N
O
N
FAD - flavin dinucleotide
(a hydride acceptor)
NH
N
H
O
N
N
N
N
FAD
H
FADH2
simplified structures for FAD and FADH2
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
4
H
H
B
N
C
B
H
C
C
H
H
N
C
N
FAD
flavin dinucleotide
(a hydride acceptor)
H
C
N
N
H
C
N
FADH2
B
H
flavin dinucleotide
(a hydride donor)
Hydride transfer reduces FAD to FADH2 which can be oxidized to FAD.
B
8. THF – tetrahdrofolate (transfer of one carbon units) –recycles cysteine to methionine and other
1C metabolic functions, many variations
Tetrahydrofolate (THF)
one carbon transfers as
"CH3", "CH2".
R
H2N
R
N
V22-p762
N
H
N
actual
structure
N
H
=
5
N
H
HN
10
Ar
simplified
structure
N
H
O
One glutamate is
shown, but several
can be attached.
HN
One carbon groups
can bond here in
various ways (see
below structures.
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
H
N
O
CO2
CO2
5
R
different forms
R
R
R
N
N
N
N
NAD+
5
NADH
N
HN
N5-methyl THF
5
-H2O
N
O
N
H2C
Ar
5
N
H
5
NADPH
N
CH3
+H2O
NADP+
10
N
HC
Ar
N ,N -methylene THF
glycine
or
serine
THF
-H2O
10
10
Ar
N10-formyl THF
Ar
H
N5,N10-methenyl THF
10
N
HCO2
ATP
+H2O
R
+NH3
R
N
-NH3
N
histidine
THF
N
THF
5
5
N
HN
H
O
HN
NH
10
H
Ar
10
Ar
N -formimino =THF
5
N5-formyl THF
9. SAM = S-adenosylmethionine (methyl transfer agent), The methyl group (CH3) attached to the
methionine sulfur atom in SAM is chemically reactive. This allows donation of this group to an
acceptor substrate in transmethylation reactions. More than 40 metabolic reactions involve the
transfer of a methyl group from SAM to various substrates, such as nucleic acids, proteins, lipids
and secondary metabolites. SAM can be made from methionine and N5-methyl THF (just above).
leaving group was triphosphate
SAM = S-adenosylmethionine
Rmet
N
methionine NH2
Rad
NH2
O
O
S
CH3
N
S
N
=
OH
simplified structure
actual
structure
Rmet = methionine
Rad = adenonine
O
NH2
O
O
P
O
O
HO
OH
adenosine
SAM = S-adenosylmethionine
O
O
P
O
N
CH3
N
O
NH2
O
P
O
N
O
S
N
N
OH
methionine
CH3
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
HO
OH
ATP
6
10. Cytochrom P-450 enzymes are oxidizing agents in the body. They can convert inert alkane sp3
C-H bonds into C-OH bonds and they can make epoxide groups at alkenes and aromatic pi bonds.
Oxidations in the body often use cytochrom P-450 enzymes.
N
N
N
+3
Fe
N
N
simplified
structure
N
simplified
structure
Fe
N
N
+3
N
Fe
N
N
N
S
S
Enz
Enz
HO2C
CO2H
heme, protoporphyrin IX, found in
cytochrom P-450 oxidative enzymes
This is the structure
that we will use.
O
+4
Fe
+3
Fe
simplified structure
11. Halogenase Enzymes (related to cytochrom P-450 enzymes, can have imidazole ligands from
histadine amino acids
Halogenations in the body often iron halogen bonds.
His
N
O
N
N
O
N
This is the structure
that we will use.
Cl
O
O
+4
Fe
+3
Fe
Fe
His
H
Cl
simplified structure
+3
N
Fe
N
+4
Cl
N
N
N
His
Biochemical Reaction Mechanism Examples
Mechanism arrows used in the “Bio-Org Game” are meant to suggest how the electrons
move over a single transformation, and are not necessarily meant to imply that all of the electrons
and atoms transfer in one huge “domino” cascade. Organic mechanisms are often multistep
transformations, but it’s harder to pin down biochemical transformations. The symbolism used in
these examples represents a concise way to show electron movement involving making and
breaking bonds. Lone pairs are rarely drawn (or used). They are included on the generic base (B:)
used to show proton transfers. A generic acid (H-B+) is used to provide a proton. Very
occasionally a pair of electrons is used when it provides some special effect (enamine reaction,
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
7
resonance stabilization in acetal formation or breakdown). Multiple resonance structures are not
drawn. Only very occasionally is an intermediate drawn, when confusion arises from too many
arrows going in too many different directions. Do not confuse these examples for real
mechanisms! They are designed to show the essential how changes might occur in complex
biochemical reactions. Also, at physiological pH (7) a few organic groups are ionized (RCO2H is
anionic as RCO2--, and RNH2 is cationic as RNH3+). They are drawn in their neutral forms in this
game. The initial examples of biochemical transformations can serve as foundational reactions in
endless biochemical sequences or cycles. Knowing how these reactions work can provide insight
into many biochemical aspects of anabolism and catabolism and can help improve your organic
“mechanistic” logic. First, bare-bones examples are provided to show the essence of each type of
reaction. The problems that follow use several “typical” types of biochemical transformations in
made-up sequences and many real biochemical cycles in which to practice. With such practice
using these simple model reactions you can learn to recognize where (when) and how similar
transformations might be occurring in real biochemical reactions that are presented without any
mechanistic detail in a book or article. Nature uses simple strategies applied to limited classes of
molecules (carbohydrates, lipids, fats, steroids, amino acids, nucleic acids, neurotransmitters,
alkaloids, terpenoids and more) having enormous variation of patterns. It’s amazing what you can
speculate upon using these few reactions.
An example of mechanistic simplification.
An “organic” arrow pushing mechanism, showing keto  enol tautomerization in acid, is
shown without simplification, having all of the normal mechanistic details (lone pairs, formal
charge, resonance, etc.). We won’t do it this way in the Bio-Org game.
H
B
O
H
C
C
O
O
O
C
H
H
H
C
H
C
B
C
H
C
C
resonance
A complete organic mechanism shows lone pairs, each individual step and resonance structures.
The same mechanism in the Bio-Organic Mechanism Game is shown in the first “biochem”
example, using the simplified mechanistic conventions of this game.
1.
Keto / enol tautomerization (two proton transfers and a shift of pi electrons).
H
B
B
H
B = general base,
possibly on enzyme
O
O
B
C
H
C
keto tautomer
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
H
C
C
enol tautomer
B
H
B = general acid,
possibly on enzyme
8
H
B
H
H
O
B
B
O
C
C
C
H
B
C
enol tautomer
keto tautomer
Quite often in biochemistry the acid and base functions are a cooperative action in the active
site of an enzyme, much in the manner used in this Game. This avoids the necessity of very strong
acid or very strong base, often used by chemists in their reactions. Such conditions are not
tolerated by living organisms. We arbitrarily use neutral base, B: and cationic acid H-B+.
2. Carbonyl hydration – a regioselective addition reaction of H2O to a carbonyl group. This also
requires some proton tranfers. A carbonyl hydrate can be dehydrated via an elimination reaction
which also requires some proton transfers. These steps are very similar to hemiacetal/hemiketal
reactions (Example 6), but use H-O-H instead of R-O-H. The carbonyl hydrate can be used to
oxidize an aldehyde (example 8) or allow a reverse aldol reaction (example 3).
Forward Direction
B
O
B
B
H
H
O
H
H
hydration
C
H
O
H
O
C
(addition
reaction)
carbonyl hydrate
aldehyde or ketone
Reverse Direction
B
B
H
H
O
O
C
H
B
H
O
dehydration
(elimination
reaction)
carbonyl hydrate
B
H
O
H
C
aldehyde or ketone
3. Aldol reactions make a new carbon-carbon bond, forming a -hydroxycarbonyl compound. A
carbonyl C position becomes the nucleophile (as enol or enolate) and reacts with a separate
electrophilic carbonyl carbon. Reverse aldol reactions cleave the C-C bond, leaving the
electrons on a C position and forming a C=O at the C-OH position. The aldol product can
proceed on an additional step as shown in Example 5 (reverse Michael  ,-unsaturated
carbonyl compounds)
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
B
9
Forward Aldol
B
B
B
H
H
C
C
C
This product also looks
like a Michael reaction.
See Example 5.
-hydroxycarbonyl
carbonyl nucleophile
at C position
carbonyl electrophile
B
C
C
C
H
O
O
aldol
(addition
reaction)
O
O
H
Reverse Aldol
B
H
H
O
O
C
C
B
reverse
aldol
(elimination
reaction)
B
B
H
O
O
H
C
C
C
C
-hydroxycarbonyl
4. Claisen reactions make a new carbon-carbon bond, forming -ketocarbonyl compounds. A
carbonyl C position becomes the nucleophile (as enol or enolate) and reacts with a separate
electrophilic carbonyl carbon (similar to Example 3, except carbonyl substitution occurs instead of
carbonyl addition). Ester groups are common in organic chemistry and thiol ester groups (acetyl
Co-A) are common in biochemistry. Reverse Claisen reactions cleave the C-C bond leaving the
electrons on the C position and forming a carboxyl at the C=O position. The tetrahedral
intermediate is omitted in the Bio-Organic Game.
Forward Claisen
H
B
B
B
O
H
C
Claisen
(acyl substitution)
C
C
OR
OR
C
R
C
H
H
B
reverse Claisen
(acyl substitution)
C
C
R
O
alcohol
or thiol
-ketocarbonyl
ester or
thiol ester
B
O
O
O
OR
O
Reverse Claisen
-ketocarbonyl
OR
B
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
B
O
alcohol
or thiol
carbonyl
nucleophile
H
C
C
H
carbonyl electrophile with
a leaving group, (often and
ester or thiol ester or a
mixed anhydride)
O
O
O
H
C
C
OR
carbonyl electrophile
with a leaving group,
(often and ester or
thiol ester)
C
OR
ester or
thiol ester
H
B
10
5. Reverse Michael reaction (elimination = dehydration) eliminates H2O between the C-C bonds
(E1cB mechanism). Dehydration carries the aldol (Example 3) one step farther along, forming
,-unsaturated carbonyl compounds. Michael reaction (addition / hydration) is the reverse
reaction and adds the elements of water across the C=C, a resonance extension of the C=O. We
have taken liberties with the name “Michael”. It is probably better to describe these reactions as
conjugate addition and reverse conjugate addition. A close variation of this reaction eliminates
alcohols instead of water. Other possibilities also exist.
Reverse Michael Reaction
B
B
H
H
O
C
O
O
C
C
C
C
C
(elimination)
H
-hydroxycarbonyl
-unsaturated carbonyl
(Michael acceptor)
B
Reverse Michael Reaction
H
B
H
H
reverse
Michael
reaction
O
H
B
O
O
O
Michael
reaction
C
C
H
H
C
C
H
C
C
(addition)
-unsaturated carbonyl
(Michael acceptor)
O
H
-hydroxycarbonyl
B
B
H
B
This product looks like
an aldol product. See
Example 3. It is now
able to do a reverse aldol,
or be oxidized to a
1,3-dicarbonyl, maybe
followed by
decarboxylation, etc.
6. Hemiacetal (or hemiketal) formation is an addition reaction to a carbonyl by alcohol, similar to
carbonyl hydration and dehydration, Example 2. The reverse reaction reforms the carbonyl group
and alcohol in an elimination reaction., A second alcohol can react with the hemiacetal/ketal and
undergo an SN1 reaction with the OH to form an acetal or ketal (Example 7, just below). The
example shown here is an intramolecular reaction and typically forms rings of 5 or 6 atoms.
Forward Direction
B
H
H
O
O
C
C
alcohol
aldehyde or ketone
H
B
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
B
addition
reaction
H
O
O
hemiacetal / hemiketal
B
11
Reverse Direction
B
H
H
B
B
H
B
H
O
O
elimination
reaction
O
O
C
C
alcohol
hemiacetal / hemiketal
aldehyde or ketone
7. Acetal (or ketal) formation from a hemiacetal (or hemiketal). The “OH” becomes a water
molecule leaving group that is replaced by an “OR” in an SN1 reaction, producing an ether linkage.
In the reverse reaction (acetal or ketal forming a hemiacetal or hemiketal) an alcohol leaving group
is replaced by a water molecule in an SN1 reaction. These are reversible reactions that require acid
catalysis. Because arrows are used in both directions on the same bonds, we show the intermediate
in this example. These reactions often occur when one sugar molecule “OH” connects to another
sugar molecule at its hemiacetal site (such as galactose + glucose = lactose). Such linkages can go
on for hundreds of sugar molecules (glycogen in animals and cellulose in plants).
Forward Direction
B
B
H
H
H
R
H
O
O
H
R
O
O
O
O
O
eliminate
H2O
hemiacetal / hemiketal
add
ROH
acetal / ketal
intermediate
Reverse Direction
H
B
B
B
H
R
O
O
O
add
H2O
eliminate
ROH
acetal / ketal
H
O
O
O
H
H
intermediate
hemiacetal / hemiketal
8. a. Oxidation of CH(OH) to C=O (1o ROH  aldehyde, 2o ROH  ketone, hydrated aldehyde 
carboxylic acid) with an equivalent of NAD+. NAD+ accepts a hydride via conjugate addition,
quenching the positive charge on the nitrogen and forms NADH. A base removes a proton from
the adjacent oxygen atom allowing an elimination reaction to produce the C=O (or in Example 9, a
C=N).
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
12
H
B
H
B
H
O
H
oxidation of
an alcohol
C
H
N
C
O
N
elimination
reaction
R
R
+
NAD
equivalent
1o or 2o alcohol
H
aldehyde or ketone
NADH
equivalent
b. Reduction of C=O to CH(OH) with an NADH equivalent is the opposite of the above reaction.
NADH is a hydride donor that becomes aromatic (forms NAD+) with the transfer of the
nucleophilic hydride to the electrophilic C=O. A nearby acid protonates the oxygen completing
the addition reaction.
B
H
H
H
H
B
H
O
reduction of
a carbonyl
C
N
addition
reaction
O
H
C
N
R
NADH
equivalent
aldehyde or ketone
1o or 2o alcohol
R
NAD+
equivalent
9. a. Oxidation of an amine, CH(NHR), to imine (C=N-R) with an NAD+ equivalent that is reduced
to NADH, followed by hydrolysis to a C=O. This is the opposite of 9b, below. The first step is
similar to reaction 8a above with an alcohol. Overall, this is a transformation of an amine into a
carbonyl group and a primary amine.
Oxidation of an amine
B
R
N
H
H
H
H
B
elimination
reaction
C
R
C
H
N
amine
R
NAD+
equivalent
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
H
N
N
oxidation of
an amine
imine
R
NADH
equivalent
13
Hydrolysis of an imine
B
B
H
H
B
H
H
R
O
N
R
H
R
O
C
elimination
reaction
addition
reaction
imine
B
H
C
C
H
N
O
N
B
H
B
H
aminal
aldehyde or ketone
b. Formation of an imine, C=N-R, from a C=O, followed by reduction to CH(NHR) (an amine)
with an NADH equivalent that is oxidized to NAD+. This is the opposite of 9a, above. The
second step is similar to reaction 8b above with an alcohol. Overall, this is a transformation of a
carbonyl group into an amine.
Formation of an imine
B
B
H
H
R
N
H
B
O
R
H
H
B
R
H
N
C
aldehyde or ketone
B
B
O
N
addition
reaction
C
H
H
elimination
reaction
aminal
O
C
H
imine
Reduction of an imine
B
H
H
H
B
R
H
H
reduction of
an imine
N
N
R
C
N
imine
R
NADH
equivalent
H
addition
reaction
C
N
amine
NAD+
equivalent
R
10. Decarboxylation of a -ketocarboxylic acid, forming an enol, which tautomerizes to a keto group.
H
O
B
B
H
O
O
C
decarboxylation
O
C
O
-ketocarboxylic acid
enol tautomer
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
B
H
C
C
C
H
C
B
H
O
O
carbon
dioxide
tautomers
C
H
C
keto tautomer
B
B
14
11. Decarboxylation of an -ketocarboxylic acid with TPP (thiamine diphosphate). Also includes
both “TPP ylid” and “TPP enamine” chemistry. The enamine can be protonated to form an
aldehyde or it can react with another carbonyl compound to make a new carbon-carbon bond (a
larger carbohydrate in this game) The TPP ylid is also regenerated, which can react again or
protonate to make TPP. See another reaction of -ketocarboxylic acids with Vit B-6 in Example
13.
TPP reaction with an a-ketoacid, decarboxylation and formation of enamine.
R
OH
R
B
N
O
H
B
R O
N
C
H
S
S
TPP
pKa  18
O
R
-ketoacid
TPP ylid
B
H
C
O
C
N
C
TPP ylid
addition to
a carbonyl
S
OH
R
decarboxylation
(-CO2)
R
OH
N
C
S
R
TPP enamine
Reaction of enamine nucleophile with a carbonyl electrophile followed by an E2-like reaction to from a new (larger)
carbohydrate.
B
R
R
R
H
H
B
O
O
OH
N
N
OH
N
C
C
S
H
R
TPP enamine
reaction with C=O
C
R
TPP enamine
addition to
a carbonyl
S
R
C
H
R
elimination
reaction forms
a carbonyl group,
similar to a
reverse aldol
S
TPP ylid
O
OH
C
R
CH
CH
R
OH
a new (larger) carbohydrate
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
15
Reaction of enamine nucleophile with an acid to from a new (smaller) carbohydrate.
B
R
R
O
N
OH
N
H
C
B
O
N
C
S
S
R
TPP enamine reaction
with a proton
R
H
R
acid/base
protonation of
TPP enamine
C
H
H
R
S
elimination
reaction forms TPP ylid
a carbonyl group,
similar to a
reverse aldol
a new (smaller)
carbohydrate
12. a. Phosphorylation of an OH with an ATP equivalent (making an inorganic phosphate ester).
O
O
O
O
O
P
O
O
O
P
O
P
O
P
O
O
C
O
O
O
O
+2
Mg
H
B
P
O
ADP
ATP
acyl-like
substitution
reaction
O
Mg+2
ADP = leaving group
O
Complexing with Mg+2 can make one phosphorous atom
more electrophilic and the other one a better leaving group.
The Mg+2 is not required to show this reaction. Mg+2
is not used in the other reactions below, but it could be.
C
O
P
O
O
H
B
inorganic phosphate ester
b. Dephosphorylation of an inorganic phosphate ester to an alcohol and phosphate.
B
H
O
C
O
P
O
H
B
inorganic
ester
hydrolysis
O
O
C
O
B
O
O
P
H
acyl-like
substitution
reaction
H
H
H
O
O
B
c. An elimination reaction of a phosphate leaving group to make an alkene (pi bond). Could
actually be E1 or E2.
O
C
O
P
O
O
E1 or E2 (anti)
mechanisms
are possible
C
C
C
B
H
O
H
O
H
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
B
H
P
O
O
16
d. acyl phosphate (inorganic anhydride) and formation of a thiol ester (like acetyl Co-A)
ADP leaving group
O
O
O
P
O
P
O
phosphate
leaving group
ADP
O
O
O
O
O
Mg+2
O
P
O
P
organic-inorganic
anhydride
ATP
O Mg+2
O
C
acyl-like
substitution
reaction
H
H3C
O
O
O
O
B
O
C
O
P
H3C
O
O
O Mg+2
acyl-like
substitution
reaction
H
B
Co-A
Co-A
S
very reactive
thiol ester
(acetyl Co-A)
S
H
B
13. Vit B-6 reactions – 1. imine formation with -keto acid and the amino version of Vit B-6 (similar
to Example 9b), 2. tautomerization (Example 1) and 3. imine hydrolysis to amino acid and the
aldehyde version of Vit B-6 (similar to Example 9a).
B
H
OH
B
H
H
O
OH
OH
O
N
N
H
-keto acid
R
B
N
H
vitamin B-6
(1o amine version)
N
O
R
O
imine
synthesis
N
H
Similar to Example 9b.
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
H
O
R
H
B
dehydration
(-H2O)
N
H
O
H
H
17
B
OH
OH
H
H
B
H
N
N
O
O
H
Similar to Example 1.
R
R
keto / enol
tautomerization,
makes imine on
the other side
N
N
H
H
B
OH
H
OH
H
H
O
BH
H
B
H
H
B
H2N
OH
O
H
H
O
N
O
N
O
O
R
H
N
N
H
H
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
hydrolysis
of imine
R
-amino acid
R
addition
of water
Similar to Example 9a.
H
N
H
vitamin B-6
(aldehyde version)
18
Three additional vit B6 reactions from aromatic imine
1. Decarboxylation
B
H
O
B
C
O
H
O
H
N
N
B
H
H
BH
H
H
N
O
R
H
O
R
H
R
decarboxylation
N
N
H
H
N
H
B
O
H
H
H
H
H
N
O
N
B
H
R
R
N
H
N
H
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
19
2. Elimination of side R group, like serine or threonine.
B
serine aa
H2C
B
H
O
H
O
H
N
H
O
B
N
H
BH
N
CO2H
CO2H
CO2H
decarboxylation
N
N
H
vitamin B-6
(imine version)
N
H
H
H
B
H
also threonine aa
O
O
O
N
H
H
H
H
N
O
N
H
H
H
CO2H
B
CO2H
N
CO2H
glycine aa
N
H
N
glycine aa
CO2H
H
H
vitamin B-6
(aldehyde version)
N
H
3. Epimerize a proton at the C position of an amino acid.
S amino acid
N
H
B
proton adds on
the opposite face
R
N
CO2H
N
H
vitamin B-6
(imine version)
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
H
B
R amino acid
N
R
R
H
CO2H
CO2H
N
N
H
H
vitamin B-6
(imine version)
20
14. FAD / FADH2 reduction of C=C to CH-CH or the reverse reaction oxidation of CH-CH to a C=C,
FAD can be recharged with NADH.
Simplified mechanism of action for reduction of C=C by FADH2
FADH2 from NADH.
FAD and mechanism for reforming
O
O
H H
CoA
R
CoA
S
R
H
H
N
S
H H
B
B
N
H
N
FADH2
B
B
N
FAD
H
H
H
H
N
N
N
N
NAD+
N
R
B
H
N
NADH
FADH2
H
R
FAD
H
H
B
N
N
FADH2 - flavin
dinucleotide
(a hydride donor)
FAD - flavin dinucleotide
(a hydride acceptor) used
to reoxidize fats for energy.
N
N
H
H
O
H
H
C
R
H
H
C
C
S
C
O
Enz
C
R
FADH2
B
A saturated fatty acid chain.
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
C
Enz
S
H
An ,-unsaturated fatty acid chain.
21
3
3
15. Cytochrom P-450 oxidation of sp C-H bonds to make sp C-OH groups
alcohols
sp3 C-H bonds
H
O
H
C
H
O
O
C
C
Fe +3
Fe +4
9
Fe +4
8
The carbon free radical abstracts hydroxyl (OH) from
iron, making an C-OH bond where a C-H bond had
been. The iron is reduced back at Fe+3 to begin the
process all over again.
The free radical-like oxygen atom abstracts
a hydrogen atom from a C-H bond in the
enzyme cavity, forming an O-H bond and a
carbon free radical.
16. Cytochrom P-450 oxidation of C=C pi bonds (alkenes and aromatics) to make epoxides, which can
be opened to diols.
R
R
R
C
R
C
C
R
C
C
R
O
O
R
R
R
R
R
C
O
R
epoxides
Fe +3
Fe +4
Fe +4
The free radical-like oxygen atom adds to a
C=C bond (alkene or aromatic) in the enzyme
cavity, forming a O-C bond and a carbon free
radical.
The carbon free radical abstracts the oxygen atom from
the iron, making an epoxide ring. The iron is reduced
back at Fe+3 to begin the process all over again. Reactive
epoxides can be opened up to diols (more water soluble).
17. Cytochrom P-450 oxidation of sulfur and nitrogen lone pairs.
S
S
R
R
O
O
sulfur
substrate
(1e-)
sulfur
substrate
Fe +4
Fe +4
N
S
R
R
R/H
N
R
R
Fe +4
Fe +3
sulfoxides, further oxidation is
possible, all the way to sulfate, SO4-2
R/H
O
O
R
R
nitrogen
substrate
(1e-)
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
O
R
nitrogen
substrate
Fe +4
O
R
Fe +3
N
R
R/H
R
N-oxides, further oxidation is
possible, all the way to nitrate, NO3-1
22
18. Halogenation of sp3 C-H bonds to make C-X groups (X = Cl, Br, I) using halogenase enzymes.
sp3 C-H bonds
H
C
O
Cl
H
C
Cl
Fe +5
The free radical-like oxygen atom abstracts
a hydrogen atom from a C-H bond in the
enzyme cavity, forming an O-H bond and a
carbon free radical.
H
O
C
O
Cl
Fe +5
Fe +4
The carbon free radical abstracts a halogen (Cl or Br)
forming an unusal halogenated bioorganic molecule.
19. Halogenations of aromatic rings using X-OH to make sp2 C-X bonds (like thyroxine).
Iodide is stored in the thyroid gland. Iodoperoxidase enzyme makes it electrophilic (instead of nucleophilic
iodide). It could react as hypoiodous acid, or the oxygen could be made into an even better leaving group if
was a phosphate (using ATP).
H
B
H
O
H
O
I
O
O
O
H
O
H
P
O
ATP
O
O
I
H
I
O
B
P
O
O
possibly an even
better leaving group
a good leaving group on iodine
Speculative mechanism for iodinating tyrosine and formation of thyroxine from two tyrosines.
O
I
B
H
I
CO2H
CO2H
H
H
NH2
H
O
NH2
O
tyrosine
I
CO2H
H
NH2
O
I
repeat
H
NH2
O
I
diiodotyrosine - makes thryoxine
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
CO2H
23
20. S-adenosyl methionine (SAM-e) to methylate biomolecules.
NH2
B
6
H
Rmet
S
H3C
N 1
5
NH2
NH2
H3C
N
H
N
2
CH3
4
Rad
N
N
O
3
N
O
O
H
H
H
5-methylcytosine
cytosine
21. Anti-oxidation reactions using vit E (fat soluble), vit C (water soluble), (also possible are
glutathione, resveratrol and other bio-antioxidants).
possible dangerous free
radical reduced by vit E
reduced radical neutralized
by body's buffer system
R
R
R
H
H
H
B
R
O
H
R
O
free radical protection by vitamin E
(possibly in cell membrane)
R
O
H
R
R
R
O
O
O
R
R
H
O
H
vitamin C reduces
vitamin E back to
normal and ultimately
washes out of the body
H
B
O
R
O
resonance and inductive
effects stabilize radical so
it does not do damage
vitamin E located
in cell membranes
quenches radicals
O
H
O
H
O
H
O
O
H
O
O
H
O
O
O
R
R
O
R
O
B
O
R
H
O
B
protects a
second time
O
O
oxidized vitamin C
form washes out
of the body
O
O
R
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
R
H
O
R
vitamin E is recharged
and still in cell membrane
24
other possible anti-oxidants
OH
glutathione
SH
NH2
O
H
O
N
N
OH
OH
HO
resveratrol
O
glutaric acid
( linkage)
H
OH
O
cysteine
glycine
3 types of problems are possible
1. Fill in the missing mechanistic details.
2. State what transformation occurred (and provide the missing mechanistic details).
3. Given the term, draw the step (and provide the missing mechanistic details).
Summary of Biochemical Topics having examples provided above:
1. Keto/enol tautomerization (proton transfer, resonance, proton transfer).
2. Carbonyl hydration (addition reaction of H2O to a C=O) / carbonyl hydrate dehydration
(elimination reaction forms a C=O and H2O).
3. Aldol (makes a -hydroxy carbonyl compound). Reverse aldol, (makes 2 C=O from a -hydroxy
carbonyl compound).
4. Claisen (makes a -keto ester). Reverse Claisen (makes two esters). Often occurs using thiol
esters in biochemistry (such as acetyl Co-A).
5. Reverse Michael reaction (elimination / dehydration) of -hydroxy carbonyl compounds, an
elimination reaction forms ,-unsaturated carbonyl compounds and carries an aldol reaction one
step farther. Michael reaction (addition / hydration) adds a nucleophile at the beta carbon of an
,-unsaturated carbonyl compound (usually OH in this game) and adds a proton at the alpha
carbon.
6. Hemiacetal (or hemiketal) formation (an addition reaction) of an alcohol to a C=O, forms an ether
and an alcohol group on the same carbon. The reverse reaction reforms the carbonyl and alcohol
from an elimination reaction. Typical ring sizes in the intramolecular reaction are 5-6 atoms.
These transformations are very similar to carbonyl hydration / dehydration, presented in example 2
above.
7. Acetal (or Ketal) formation from a hemiacetal (or hemiketal) makes a water molecule leaving
group that is replaced by an alcohol in an SN1 reaction, producing a second ether linkage. In the
reverse reaction (acetal or ketal forming a hemiacetal or hemiketal) an alcohol leaving group is
replaced by a water molecule in an SN1 reaction. Both are reversible reactions. Because arrows
are used in both directions on the same bonds, we show the intermediate in this reaction.
8. a. Oxidation of CH(OH) to C=O with an NAD+ equivalent, which is reduced to NADH (opposite
of 8b, below).
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
25
+
b. Reduction of C=O to CH(OH) with an NADH equivalent, which is oxidized to NAD (opposite
of 8a, above).
9. a. Oxidation of an amine, CH(NHR), to C=N-R (an imine) with an NAD+ equivalent which forms
NADH, followed by imine hydrolysis to a C=O (opposite of 9b, below).
b. Formation of an imine, C=N-R, from a C=O, followed by reduction to CH(NHR) (an amine)
with an NADH equivalent which forms NAD+ (opposite of 9a, above).
10. Decarboxylation of a -ketocarboxylic acid, liberates CO2 and forms an enol which tautomerizes
to a keto group.
11. Decarboxylation of an -ketocarboxylic acid with TPP (thiamine pyrophosphate = diphosphate).
The “TPP ylid” adds to an -keto group, liberates CO2 and becomes a “TPP enamine”, which can
protonate or react with a C=O of another carbohydrate.
12. a. Phosphorylation of an OH with an ATP equivalent (making a phosphate ester) – common in
enzyme signaling
b. Dephosphorylation of a phosphate ester to an alcohol and phosphate – common in enzyme
signaling
c. Making an alcohol OH into a phosphate ester makes it a better leaving group. An elimination
(E1 or E2) or substitution (SN2) reaction with a phosphate leaving group is possible.
d. Formation of acyl phosphates (mixed anhydrides) also allows for exothermic carbonyl
substitution reactions (can make thiol esters).
13. Vit B-6 reactions – Many reactions are possible. The only example shown is 1. imine formation
with an -keto acid and the primary amine version of Vit B-6, 2. tautomerization to a different
imine, and 3. imine hydrolysis to an amino acid and the aldehyde version of Vit B-6. The imine
complex also allows for the loss of various groups on amino acids (the acid part, CO2H, an alpha
C-H proton, and certain amino acid side groups, -CH2OH in serine, and -CHCH3OH in threonine).
Imines are also seen in Example 9 and -keto acids in Example 11.
14. FAD / FADH2 reduction of C=C to CH-CH or the reverse reaction oxidation of CH-CH to a C=C,
FAD can be recharged with NADH.
15. Cytochrom P-450 oxidation of sp3 C-H bonds to make sp3 C-OH groups.
16. Cytochrom P-450 oxidation of C=C pi bonds (alkenes and aromatics) to make epoxides, which can
be opened to diols.
17. Cytochrom P-450 oxidation of sulfur and nitrogen lone pairs.
18. Halogenation of sp3 C-H bonds to make C-X groups (X = Cl, Br, I) using Fe halogenase enzymes.
19. Halogenations of aromatic rings using X-OH to make sp2 C-X bonds (X = Cl, Br, I) (thyroxine).
20. S-adenosyl methionine (SAM-e) to methylate biomolecules.
21. Anti-oxidation reactions using vit C, vit E, resveratrol, glutathione, and other bio-antioxidants.
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
26
Many of the steps of biochemical cycles can be explained with the above reactions.
Problem – Use B-H+ / B: and any necessary cofactors to accomplish the following transformations
using simplistic mechanisms (you do not need to show lone pairs of electrons and you can
combine multiple steps using several arrows).
1.
H
H
O
H
O
O
H
O
O
H
O
O
H
reverse
aldol
reverse those steps,
do a forward aldol
(acyl
substitution
reaction)
(acyl
substitution
reaction)
hemiacetal
formation
6 atom ring
reverse that reaction
back go a carbonyl
and an alcohol
2.
H
H
O
H
O
O
H
O
O
H
O
(addition
reaction)
O
(elimination
reaction)
H
3.
H
H
O
H
O
H
O
O
reverse
Michael
(dehydration)
O
O
H
O
H
(elimination
reaction)
forward
Michael
(hydration)
(addition
reaction)
4.
H
H
O
H
O
H
O
O keto/enol
tautomerization
to form an
aldehyde
(twice)
O
O
H
O
carbonyl
(hydration)
(addition
reaction)
H
5.
H
H
O
H
O
H
O
O keto/enol
tautomerization
to form a new
ketone
(twice)
O
O
H
O
H
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
hemiacetal
formation
5 atom ring
(addition
reaction)
27
6.
OH
OH
O
keto/enol
tautomerization
to form a beta
keto acid
OH
OH
decarboxylation
OH
keto/enol
tautomerization
to form an
aldehyde
NAD+
oxidation
carbonyl
(hydration)
(elimination
reaction)
(addition
reaction)
7.
OH
OH
O
keto/enol
tautomerization
to form an alpha
keto acid
OH
OH
reaction with
TPP ylid
(addition
reaction)
OH
decarboxylation
to TPP enamine
elimination
reaction to
form new 6C
carbohdrate
and TPP ylid
TPP enamine reaction
with 2C carbohydrate
O
H
OH
(addition
reaction)
8.
OH
O
O
R
reverse
Claisen
forward
Claisen
O
(acyl substitution
reaction)
OH
(acyl substitution
reaction)
9.
OH
OH
O
NADH
reduction
NAD+
oxidation
to an aldehyde
H
OH
OH
(addition
reaction)
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
(elimination
reaction)
28
10.
H
O
HO
O
HO
acetal
formation
(2 steps)
O
(addition
reaction)
(elimination
reaction)
OH
R
H
overall = SN1
intermediate
11.
O
R
HO
O
HO
acetal
hydrolysis
to hemiacetal
(2 steps)
H
(elimination
reaction)
OH
H
O
intermediate
(addition
reaction)
12.
Vit B-6
imine
formation
(2 steps)
O
OH
(addition
reaction)
O
(elimination
reaction)
13.
O
OH
N
keto/enol
tautomerization
to new imine
hydrolysis of
imine to amino
acid and the
aldehyde version
of Vit B-6 (2 steps)
(addition and
elimination
reactions)
N
H
14.
H
OH
N
O
H
H
OH
R
imine
formation
(2 steps)
(addition and
elimination
reactions)
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
NADH
reduction
to an amine
(addition
reaction)
overall = SN1
29
15.
R
H
N
OH
NAD+
oxidation
to an imine
imine
hydrolysis
to an aldehyde
(2 steps)
(elimination
reaction)
(addition and
elimination
reactions)
H
OH
16.
H
O
O
O
P
PP
O
ATP
O
OH
phosphorylation of
3o alcohol withATP
(acyl-like
substitution
reaction)
17.
O
O
elimination
reaction to
form an alkene
alcohol (show
as an E2 reaction)
P
O
O
OH
H
18.
O
O
P
O
O
hydrolysis of
phosphate ester
to di-alcohol
OH
(acyl-like
substitution
reaction)
H
19.
O
O
O
H
P
PP
O
ATP
O
formation
of mixed
anhydride
(acyl-like
substitution
reaction)
O
20.
O
O
P
O
Claisen
condensation
O
O
H
OH
Co-A
S
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
(acyl-like
substitution
reaction)
30
21.
O
O
Co-A
NADH
reduction
of keto group
(addition
reaction)
S
22.
H
O
O
Co-A
reverse
Michael
reaction
S
(elimination
reaction)
23.
O
Co-A
S
NADH hydride
reduction of the
conjugated C=C
by a Michael
reaction
(addition
reaction)
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
31
Methylates choline, norepinephrine, DNA (epigenetics)
Biotin (carboxylations)
Lipoic acid (acyl transfer)
Possible reactions
Aldol
reverse Aldol
Hemi-acetal formation
reverse hemi-acetal reaction (includes ketal reactions)
Acetal formation
reverse acetal reaction (includes ketal reactions)
Michael reaction
reverse Michael reaction
Carbonyl hydration reaction
carbonyl dehydration reaction
Tautomeric changes (keto  enol and/or enol  keto) (enamine chem.?)
DNA / RNA base synthesis and degradation
Additional possibilities???
Enamine chemistry
Imine chemistry
Amine oxidation to carbonyl
Phosphate ester / anhydride synthesis and hydrolysis (tyrosine, serine, ATP, throxine, etc.)
xxxxxxxxxx
Lipid chemistry – glycerol esters, ethers, phosphates, carbohydrates
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
32
B
Forward Direction
B
H
H
H
B
H
H
O
O
C
C
alcohol
aldehyde or ketone
B
R
H
O
O
B
H
R
O
O
O
O
O
add
ROH
lose
H2O
hemiacetal / hemiketal
acetal / ketal
intermediate
Reverse Direction
H
B
H
B
B
R
B
O
O
O
H
B
H
H
O
O
O
lose
ROH
add
H2O
acetal / ketal
H
O
O
C
C
alcohol
hemiacetal / hemiketal
intermediate
B
H
aldehyde or ketone
B
Forward Direction
B
H
H
H
B
H
H
O
O
C
C
alcohol
aldehyde or ketone
B
O
O
R
H
O
B
H
O
O
lose
H2O
hemiacetal / hemiketal
intermediate
add
ROH
R
O
O
acetal / ketal
B
Reverse Direction
H
B
H
R
B
B
B
O
H
H
H
O
O
O
O
O
lose
ROH
acetal / ketal
add
H2O
hemiacetal / hemiketal
intermediate
H
H
O
O
C
C
alcohol
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
B
aldehyde or ketone
33
Problem - What kind of reaction occurred in each part? Use a simplistic mechanism to show how
the reaction could have proceeded. The following problems are more limited questions from the
original “carbohydrate game” and do not include many of the biochemical “co-factors”.
OH
O
O
O
1?
OH
OH
H
OH
OH
O
O
O
OH
OH
OH
OH
2?
H
OH
OH
OH
OH
OH
OH
OH
OH
O
OH
OH
OH
O
O
OH
OH
O
3?
OH
OH
HO
HO
OH
OH
OH
HO
OH
OH
OH
OH
HO
OH
OH
O
OH
OH
OH
O
OH
6?
OH
OH
OH
HO
5?
OH
O
OH
OH
O
HO
4?
OH
O
OH
7?
OH
OH
OH
O
OH
H
8?
OH
O
OH
OH
O
9?
OH
O
H
12 ?
(2 steps)
O
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
OH
11 ?
H
O
O
10 ?
O
34
O
OH
OH
OH
OH
H
OH
OH
13 ?
OH
OH
OH
OH
OH
2
rotations
14 ?
(2 steps)
OH
O
O
OH
O
HO
OH
OH
O
H
H
O
O
OH
18 ?
HO
HO
O
O
O
O
OH
17 ?
HO
O
O
15 ?
H
OH
OH
16 ?
HO
OH
O
O
1. reverse aldol
7. keto/enol tautomerization
13. 2 x keto/enol tautomerization
2. forward aldol
8. reverse aldol
14. reverse Michael reaction
3. hemi-ketal formation to 6 atom ring
9. keto/enol tautomerization
4. reverse of hemi-ketal to 5 atom ring
10. structure shown below
5. reverse of hemi-ketal to form open chain
11. keto/enol tautomerization
15. intramolecular Michael reaction using
the OH of an alcohol group
16. reverse Michael on the other side of
the ring
17. keto/enol tautomerization
6. reverse Michael reaction
12. 2 x keto/enol tautomerization
18. reverse Michael reaction
OH
OH
O
enol at both ends of the
double bond, can form a
carbonyl on either side,
one as a ketone and one
as an aldehyde
Problem – Use B-H+ / B: to accomplish the following transformation using simplistic mechanisms
(you do not need to show lone pairs of electrons and you can combine multiple steps using several
arrows).
OH
OH
OH
dehydration
(reverse Michael)
OH
OH
OH
O
OH
OH
reverse aldol to 3C
aldehyde and 4 carbon
2,3-diketo structure
OH
OH
dehydration
(reverse Michael)
OH
keto/enol to form
1,2-diketo structure
O
OH
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
keto/enol to form
3,4-diketo structure
reverse aldol to 1C
aldehyde and 6 carbon
2,3-diketo structure
35
OH
OH
OH
hemi-acetal formation
to 5 atom ring
OH
OH
OH
O
OH
OH
OH
hemi-acetal formation
to 6 atom ring
OH
OH
O
OH
acetal formation
with ROH
OH
OH
O
H
OH
acetal formation
with ROH
OH
dehydration
to form carbonyl
keto/enol to form
2-keto structure
O
H
H
O
HO
O
OH
hemi-acetal
ring opening
HO
OH
O
HO
Michael addition
of water (hydration)
O
cyclic ester ring opening
addition of water (hydration)
OH
OH
OH
OH
OH
reverse
aldol
OH
O
forward aldol
(reverse step)
O
H
OH
OH
OH
OH
hemi-ketal formation
to 6 atom ring
O
OH
O
H
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
reverse reaction back to
carbonyl and alcohol
carbonyl
hydration
36
OH
OH
OH
HO H
dehydration
(reverse Michael)
O
OH
hydration
(Michael)
O
H
OH
OH
OH
OH
H
H
OH
OH
OH
OH
OH
OH
OH
keto/enol
tautomerization
(form a ketone)
(2 steps)
OH
OH
reverse aldol to form
a 3 carbon ketone and
4 carbon aldehyde
O
OH
hydration of
carbonyl
OH
reverse
aldol
O
HO H
OH
OH
keto/enol
tautomerization
(form an aldehyde)
(2 steps)
O
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
dehydration of
carbonyl hydrate
37
A few possible answers
OH
OH
OH
OH
OH
OH
OH
H
reverse
aldol
OH
O
O
B
H
OH
OH
O
B
OH
OH
B
OH
B
OH
hemiacetal
formation
(6 atom ring)
B
B H
H
dehydration
(reverse Michael)
OH
OH
OH
O
H
OH
O
OH
O
OH
OH
OH
O
H
B
OH
OH
OH
OH
B
OH
OH
H
OH
O
OH
O
B
OH HO H
reverse reaction
back to carbonyl
& alcohol
OH
B
OH
OH
OH
O
H
OH
H
O
H
OH
O
O
B H
OH
OH
forward aldol
(reverse steps)
H
OH
H
OH
H
OH HO H
hydration
(Michael)
OH
O
OH
OH
O
OH
O
H OH
B
B
OH
OH
OH
OH
OH
H
H
OH
OH
B
O
keto/enol
tautomerization
(form an aldehyde)
OH
OH
OH
O
H
OH
OH
keto/enol
tautomerization
(form a new ketone)
OH
OH
OH
OH
OH
O
OH
OH
OH
OH
OH
OH
OH
OH
O
B
H
OH
H OH
B H
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
OH
B
H
OH
OH
O
OH
OH
OH
OH
reverse reaction
dehydration of OH
diol
OH
OH
B
OH
hydration of
carbonyl
OH
OH
B
B H
OH
OH
O H
H
OH
O
OH
B H
B
OH HO H
OH
H
OH
B H
OH
H
O
O
OH
OH
H
H
B
OH
OH
O
38
Problem - State what type of transformation occurred and show a simplistic arrow pushing
mechanism for how it occurred, adding in any B: and/or B-H+ that is necessary. (an older problem
set)
OH
a.
OH
OH
OH
O
H
H
O
OH
O
H
H
H
O
OH
b. OH
O
OH
OH
OH
OH
OH
OH
O
O
OH
OH
OH
HO
O
c.
O
OH
OH
OH
OH
OH
O
OH
HO
OH
OH
OH
OH
O
OH
OH
OH
OH
H
OH
OH
d.
OH
OH
OH
OH
OH
OH
H O
OH
O
OH
OH
HO
OH
OH
OH
O
OH
HO
O
OH
OH
OH
OH
OH
OH
H
OH
OH
H
O
H
O
O
H
O
O
HO
H
HO
HO
OH
O
H
OH
R O
HO
OH
O
HO
OH
OH
OH
H
H
O
O
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
O
H
OH
OH
OH
OH
HO
O
R
HO
OH
OH
OH
O
OH
intermediate
OH
O
HO
OH
O
OH
HO
OH
intermediate
O
HO
R O
H
HO
OH
HO
O
O
HO
H
HO
R
R
OH
HO
intermediate
OH
R O
HO
O
OH
OH
HO
O
OH
HO
HO
HO
OH
O
O
g.
OH
H
OH
HO
OH
O
O
OH
OH
H
HO
O
i.
O
OH
OH
H
h.
O
O
O
OH
OH
HO
OH
e.
OH
f.
O
OH
HO
O
O
O
OH
OH
HO
HO
HO
OH
OH
OH
O
OH
OH
OH
H
O
HO OH
H
O
O
39
Partial Answers
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
40
OH
a.
OH
OH
OH
O
H
H
O
OH
b. OH
reverse
Michael
OH
OH
OH tautomerism
O
OH
O
OH
c.
Michael
OH
OH
OH
O
OH
OH
O
O
OH
OH
OH
HO
hemi-acetal
formation
OH
OH
H
reverse
aldol
OH
HO
O
O
H
H
OH
OH
O
OH
OH
O
OH
OH
OH
OH
H
OH
OH
d.
tautomerism
OH
OH
OH
OH
OH
OH
OH
O
O
OH
reverse
Michael
OH
OH
O
OH
O
OH
HO
O
OH
OH
OH
OH
HO
aldol
O
OH
OH
reverse
aldol
OH
HO
O
OH
hemi-acetal
formation
OH
OH
OH
OH
OH
OH
R
O
H
O
H
OH
O
O
O
HO
OH
reverse acetal
formation
(2 steps)
OH
intermediate
OH
OH
O
O
O
y:\files\classes\Organic Hunger Games\Bio-Org Game newer.doc
OH
intermediate
HO
HO
O
H
carbonyl
hydration
O
R O
H
R
O
H
O
OH
HO
R O
HO
acetal
formation HO
(2 steps)
O
OH
HO
acetal
formation
(2 steps)
OH
HO
OH
H
H
reverse
OH aldol
O
HO
H
R
OH
HO
OH
OH
HO
O
OH
HO
intermediate
H
reverse acetal
formation
(2 steps)
HO
O
OH
acetal
formation
(2 steps)
HO
HO
H
O
OH
R O
HO
O
OH
HO
OH
HO
HO
hemi-acetal
formation
O
acetal
OH formation
(2 steps)
HO
O
OH
H
O
g.
OH
H
OH
HO
OH
OH
H
O
i.
O
tautomerism O
O
dehydration
H
h.
HO
OH
e.
OH
f.
O
OH
HO
O
H O
OH
OH
HO
HO
HO
tautomerism
OH
reverse
hemi-acetal
formation
OH
OH
O
OH
OH
OH
OH
O
OH
OH
OH
H
O
HO OH
H
carbonyl
dehydration
O
O