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IOM 2018, Теория — Задача 4. Synthesis of vitamin C

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3rd Olympiad of Metropolises — Chemistry, Theoretical Problems, Official English version · 5 септември 2018 г.

Original cover

Country ______

Participant code ______

3rd Olympiad of Metropolises

Chemistry

Theoretical Problems

September 5, 2018

Moscow, Russia

Chemistry. Theoretical problems. Official English version

Указания

Begin only when the START command is given. You have 4 hours to work on the problems.
Use only the pen and calculator provided.
All results must be written in the appropriate boxes within the text. Anything written elsewhere will not be graded. Use the reverse of the problem pages if you need scratch paper.
Write relevant calculations in the appropriate boxes when necessary. If you provide only correct end results for complicated questions, you will receive no score.
Raise your hand if you have any questions concerning the text of the problems.
Raise your hand if you need a restroom break.
The official English version of this examination is available on request only for clarification.

Recommendations

Read the text carefully. Try to understand properly: a) what is given to you, b) what is required from you.
All the problems contain questions of various complexity including very simple ones. Try to answer as many questions as you can. Try to leave as few empty spaces in the answer sheets as you can.
In the calculations, use the atomic masses from the Periodic table given to you.

Good luck!

Original key cover

3rd Olympiad of Metropolises

Chemistry

Theoretical Problems

Answers, solutions, and grading scheme

September5,2018

Moscow,Russia

Chemistry. Theoretical problems. Official English version

Условие

Problem 4. Synthesis of vitamin C (12 marks)

Question	1	2	3	4	5	6	Total
Points	14	4	2	16	8	6	50
Result

The problem of healthy eating is extremely important in modern metropolises, since many inhabitants of big cities regularly eat deeply processed food and semi-finished products lacking essential nutrients. Vitamin C, or L-ascorbic acid (see the formula at the end of the first reaction scheme), is one of these. Man cannot synthesize this substance and must get it with food. In this task, we will consider different pathways of L-ascorbic acid synthesis.

Biosynthesis of vitamin C typically starts with D-glucose or its mono-phosphorylated derivatives. Transition from D- to L- sugar family achieved in different ways is one of the key steps towards the target product.

An important pathway affording vitamin C typical of most animals and plants is shown in the hereunder scheme (UMP, UDP and UTP are uridinemono-, di-, and triphosphate, $\mathrm{P_i}$ and $\mathrm{PP_i}$ are inorganic phosphate and pyrophosphate, $\mathrm{NAD^+}$ and NADH are oxidized and reduced forms of co-enzyme nicotinamide adenine dinucleotide, respectively):

Native vitamin C biosynthetic pathway, coenzymes and D-glucose-1-phosphate and L-ascorbic-acid molecular projections

1 Draw the Fischer projections of A–C and the Haworth projections of D–G. Note that all steps at the scheme are reaction equations; C and D have the same molecular formula; F, G, and vitamin C contain the same number of oxygen atoms; all the stages but the last (which is tautomerization) are enzymatically catalyzed.

Original blank response grid for Fischer projections A–C and Haworth projections D–G

[14 т.]

Notes about Fischer projections.

A. By definition, the most oxidized group is written atop a projection.

B. If a chemical reaction results in a product with the most oxidized group on the bottom, whereas the rest oxygen-containing groups are hydroxyl ones, the projection must be rotated by $180^\circ$ in the projective plane.

2 Suppose D-glucose-6-phosphate (A) or D-glucose (B) is used as the starting substance instead of D-glucose-1-phosphate. Draw the product(s) expected as a result of reaction(s) of each starting substance with $\mathrm{NAD^+}$ in systems containing all enzymes needed for corresponding redox reaction(s).

A)	B)
______	______

[4 т.]

3 What would be the product of UDP-D-glucose transformation, if one (instead of two) $\mathrm{NAD^+}$ equivalent enters into the reaction?

______ [2 т.]

Vitamin C is industrially produced via Reichstein-Grussner process (see the hereunder scheme) with D- to L-sugar family transition occurring at one of the initial stages. The starting D-glucose is first catalytically reduced to the hexabasic alcohol D-glucitol (K), which can be also considered as L-sorbitol (L) due to specific features of its structure. The next step catalyzed by bacteria Acetobacter suboxydans results in L-sorbitol oxidation to L-sorbose (M), which turns out to be a ketose. A chain of subsequent chemical transformations affords L-ascorbic acid.

Original Reichstein-Grussner industrial vitamin C synthesis, catalysts, coenzymes and intermediates K–R

4 Draw the Fischer projections of K–M, Q, R and the Haworth projections of N, O, P.

Original blank molecular response grid K–R

[16 т.]

The described above synthesis is not cost-effective, thus researches do not give up trying to develop a more efficient biotechnological process of L-ascorbic acid production. It was found that L-sorbosone, an L-sorbose derivative containing two carbonyl groups (at the $1^{\mathrm{st}}$ and $2^{\mathrm{nd}}$ positions), is the key intermediate in the pathway leading to vitamin C if bacteria Ketogulonicigenium vulgare is used.

5 Draw all possible pyranose and furanose forms of L-sorbosone. Hint: the Haworth projections of pyranose and furanose forms of D-glucose are given at the end of the task.

Pyranose form(s)	Furanose form(s)
______	______

[8 т.]

6 Suggest a synthetic scheme leading from L-sorbosone to L-ascorbic acid if it is known that one of the forms from question 5 is the pathway intermediate. Note that the latter is transformed into the target product in two steps, the enzymatic one being followed by the spontaneous one.

______ [6 т.]

Note. If you failed to deduce the L-sorbose formula in question 4, use the L-fructose one (given hereunder) to answer the questions 5 and 6.

Reference information. Haworth projections of cyclic forms of $\alpha$ -D-glucose and $\alpha$ -L-fructose.

Native complete reference table of alpha-D-glucose pyranose and furanose forms and alpha-L-fructose

Решение

Exact original key biosynthetic pathway of vitamin C, including UDP-glucose and both L-ascorbic-acid projections; native key drawing retained separately from question source

Official answers and grading scheme

Exact native A–G answer table, A–C cyclic Haworth-type drawings and D–G Fischer-type drawings, all charges, UDP/phosphate groups and bonds

2 pts for each structure. [14 т.]

Exact original redox product answer cells A and B, one phosphate-substituted structure and two nonphosphorylated structures

2 pts for each structure. [4 т.]

Native one-NAD-equivalent UDP-D-glucose product drawing, aldehyde oxygen and complete cyclic and UDP groups

[2 т.]

Complete original K–R vitamin C industrial synthesis answer grid with Fischer projections and protected Haworth structures, charged carboxylate groups and stereochemical bonds

2 pts for each structure. [16 т.]

Native pyranose and furanose L-sorbosone forms, complete four Haworth drawings and table labels

The same forms in the Fischer projections

Native same four L-sorbosone pyranose and furanose forms in Fischer projections with all cyclic oxygen bonds

2 pts for each correct form in any projection. [8 т.]

Native complete oxidation and spontaneous tautomerization scheme from furanose L-sorbosone to L-ascorbic acid

6 pts for the correct scheme. [6 т.]

Comments from the author

1 UDP-D-glucose is subjected to a 4-electron oxidation without C-C bond cleavage (there 6 carbon atoms in vitamin C). Oxidation of the $6^{\mathrm{th}}$ hydroxyl group to the carboxylic one resulting in the formation of UDP-derivative of D-glucuronic acid turns out to be the only possibility. This is followed by elimination of the UMP and phosphate residues as well as the cycle opening and selective reduction of the carbonyl group to hydroxyl one, which results in the transition to L-family (L-gulonic acid). The reaction sequence is completed by lactonization, oxidation of one of the hydroxyl groups and tautomerization.

2 The carbonyl group is the only one in D-glucose-6-phosphate that can be oxidized affording 6-phospho-D-gluconate. The carbonyl group will also be the main target in the case on non-phosphorylated D-glucose. Still, definite fraction of the monosaccharide molecules will be converted into D-glucuronic acid due to the presence of enzymes with different specificity and existence of D-glucose mostly in pyranose form in an aqueous solution. It should be mentioned that oxidating power of $\mathrm{NAD^+}$ is insufficient for oxidation of two groups (in the $1^{\mathrm{st}}$ and $6^{\mathrm{th}}$ positions) affording D-glucaric acid.

3 2-Electron oxidation of the hydroxyl group to carbonyl one will be observed if one $\mathrm{NAD^+}$ equivalent enters into the reaction. Due to the reasons similar to those considered in question1, the $6^{\mathrm{th}}$ group is the only oxidation target.

4 D-Glucose reduction leads to the hexabasic alcohol. It is impossible to find the most oxidized group in this substance, thus it can be presented in two projections, one belonging to D-, and the other to L-family. Selective oxidation of L-sorbitol leads to the ketose L-sorbose. Treatment of the letter with two equivalents of acetone allows protection of four hydroxyl groups in the furanose form of the monosaccharide. Further oxidation affords 2-keto-L-gulonic acid. Tautomerization and lactonization of the latter finally gives vitamin C.

5 L-sorbosone will give pyranose forms if the $1^{\mathrm{st}}$ group interacts with the $5^{\mathrm{th}}$ one, and the $2^{\mathrm{nd}}$ group interacts with the $6^{\mathrm{th}}$ one. Furanose forms can be obtained if the $1^{\mathrm{st}}$ group interacts with the $4^{\mathrm{th}}$ one, and the $2^{\mathrm{nd}}$ group interacts with the $5^{\mathrm{th}}$ one.

6 Only furanose form of L-sorbosone formed by interaction of the $1^{\mathrm{st}}$ and $4^{\mathrm{th}}$ groups can by transformed into L-ascorbic acid in two steps. First, the semi-acetal bond is transformed into the ester one (the carbonyl group oxidation to carboxylic one), which is followed by tautomerization affording vitamin C.

Бележка от източника

Each native problem heading says 12 marks, while its printed score grid totals 65, 30, 18, 50 or 30. Problem1 request3 is 10 points in the grid but5 in the key; its printed permanganate equation and sodium-containing answer to request2 remain literal. Problem3 first Claus-stage equation prints2H2O. Problem4 requests Fischer projections A–C and Haworth D–G, while its key shows the opposite projection types; request2 awards2points for each of three structures despite its4-point grid. Problem5 methane price is0.75 $/kg in the question and0.70$ /kg in the repeated key request and calculations. These original inconsistencies are retained. Molecular drawings, reaction schemes, reference tables and answer grids reproduce the native originals. Empty calculation spaces retain their printed labels and blank response fields.

Оригинал в Архива: Problems.pdf · официални решения: Solutions.pdf