Degradation of unprotected aldohexonic acids to aldopentoses promoted by light and oxygen

Article abstract of DOI:10.1246/CL.200517

Herein reported is a photoredox-catalyzed oxidative degradation reaction of unprotected aldohexonic acids, which are shortened by one-carbon to the corresponding aldopentoses. Oxygen including aerial oxygen is used as a terminal oxidant. The mild reaction conditions permit even disaccharides to successfully undergo the degradation reaction with the glycosidic bond remaining intact. Quinic acid is also converted to a useful chiral synthetic intermediate.

Full text of DOI:10.1246/CL.200517

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Degradation of Unprotected Aldohexonic Acids to Aldopentoses
Promoted by Light and Oxygen
Yusuke Masuda, Misato Ito, and Masahiro Murakami*
Advance Publication on the web August 20, 2020
doi:10.1246/cl.200517
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1
Degradation of Unprotected AldohexonicAcids to Aldopentoses
Promoted by Light and Oxygen
Yusuke Masuda, Misato Ito, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510, Japan
E-mail: murakami@sbchem.kyoto-u.ac.jp
1
2
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8
9
Herein reported is a photoredox-catalyzed oxidative
43 oxidant (Figure 2). The starting carboxylic acid derivatives
44 are shortened to aldopentoses through decarboxylation. Not
45 only monosaccharides but also disaccharides and other -
46 hydroxycarboxylic acids in general participate in the
47 degradation reaction. The present method avoids strong
48 oxidants or metal catalysts, instead utilizes visible light and
49 oxygen, which are readily available, non-hazardous, and
50 environmentally innoxious.7
degradation reaction of unprotected aldohexonic acids,
which are shortened by one-carbon to the corresponding
aldopentoses. Oxygen including atmospheric one is used as
a terminal oxidant. The mild reaction conditions permit
even disaccharides to successfully undergo the degradation
reaction with the glycosidic bond remaining intact. Quinic
acid is also converted to
intermediate.
a useful chiral synthetic
51
10 Keywords: sugar, degradation, oxygen, photocatalyst
11 Pentoses, i.e., monosaccharides comprised by five
12 carbon atoms play a number of important roles not only in
13 biology but also in food and pharmaceutical industries
14 (Figure 1). For example, D-deoxyribose and D-ribose are
15 the repeating units of the backbones of vital DNA and RNA,
16 respectively. D-Ribose is contained also in riboflavin
17 (vitamin B2). Xylitol produced by hydrogenation of xylose
18 has come into wide use as a sugar substitute.1 There are a
19 series of anti-cancer drugs such as cytarabine, fludarabine,
20 and nelarabine, which all contain D-arabinose.2 Some of
21 these pentoses are difficult to obtain in nature, and therefore,
22 it has been desired to derivatize readily available naturally
23 occurring compounds, hexoses for example, into pentoses.3
24 There are a diverse range of hexose derivatives abundantly
25 available from natural sources, and a convenient and
26 practical way to access pentoses is given by degradation of
27 hexoses. For example, the Ruff degradation reaction, which
28 uses hydrogen peroxide as an oxidant along with a copper or
29 iron catalyst, degrades calcium D-gluconate to D-arabinose
30 through decarboxylation.4 Alternatively, a decarboxylation
31 reaction of a gluconate salt into D-arabinose is carried out
32 by an electrochemical method,5 which is implemented even
33 on an industrial scale.6 However, it would provide a more
34 sustainable method of degradation of hexose derivatives if
35 gaseous oxygen, hopefully atmospheric one, can be used as
36 an oxidant, dispensing with the need of a metal catalyst,
37 hydrogen peroxide, electrolyte, and electricity.
52
53 Figure 2. Degradation of gluconate salts
54
We initially found that a combination of an acridinium
55 photocatalyst, visible light, and gaseous oxygen effectuated
56 a decarboxylation reaction of -hydroxycarboxylic acids
57 (Scheme 1).8 For example, 4-methoxymandelic acid (1) in
58 acetonitrile was irradiated with blue light (470 nm) in the
59 presence of 9-mesityl-10-methylacridinium perchlorate9 (2,
60 5 mol%) and KOH (20 mol%) under an atmospheric
61 pressure of oxygen for 18 h. After purification by silica gel
62 chromatography, p-anisaldehyde (3) was isolated in 76%
63 yield.10 Other photoredox catalysts such as eosin Y and
64 iridium-based complexes failed to give 3.
65
38
66
67 Scheme 1. Photo-degradation of mandelic acid 1
68
A mechanism which would reasonably explain the
69 formation of the aldehyde 3 from the carboxylic acid 1 is
70 shown in Scheme 2. It has been reported that the acridinium
71 salt 2 catalyzes an oxidative decarboxylation reaction of
72 pivalic acid to form t-butyl hydroperoxide upon
73 photoirradiation, albeit limited to this single example.11 We
74 assume that a similar mechanism would operate up to the
75 formation of peroxy anion G. Initially, carboxylic acid 1 is
76 deprotonated by a base. The resulting carboxylate anion A
39
40 Figure 1. Products containing pentoses
41
Herein reported is a photoredox-catalyzed degradation
42 reaction of aldohexonic acids using oxygen as a terminal

2
red
1
2
3
4
5
6
7
8
9
(E1/2 = +1.39 V vs SCE for sodium gluconate)12 transfers
1
2
64%
41%
single electron to the photoexcited catalyst B (E1/2red = +2.06
V vs SCE)13 to generate the carboxy radical C and the
reduced photocatalyst D. Decarboxylation of C gives rise to
the hydroxycarbon radical E, which captures oxygen to
furnish peroxy radical species F. The reduced photocatalyst
D transfers a single electron to the generated peroxy radical
F, forming peroxy anion G and the photocatalyst 2. Finally,
hydrogen peroxide anion eliminates to afford the carbonyl
10 product 3.14
11
3
62%
40%
4
12
a
42
Reaction conditions: aldonolactone (0.20 mmol), 2 (8.2 mg, 0.02
13 Scheme 2. Proposed reaction pathway.
43 mmol, 10 mol%), LiOH (4.8 mg, 0.20 mmol, 1.0 equiv), O2 (balloon),
b
44 MeCN (1 mL), H2O (1 mL), LED lamp (470 nm), rt, 18 h. Isolated
45 yield.
46
14
We have been applying the photocatalysis chemistry to
15 unprotected sugars dissolved in hydrous solvents to develop
16 their straightforward transformations.15
With the
47
Thus, unprotected monosaccharides were successfully
17 preliminary result mentioned above in hand, we next
18 examined an analogous degradation reaction using an
19 unprotected sugar lactone, D-glucono-1,5-lactone (4) (Table
20 3, entry 1). D-Glucono-1,5-lactone (4), photocatalyst 2 (10
21 mol%), and LiOH (1 equiv) were dissolved in
22 acetonitrile/water (1/1) and irradiated with blue light (470
23 nm) under an atmospheric pressure of oxygen for 18 h.
24 After the solvent was removed under reduced pressure, the
25 residue was subjected to silica gel chromatography and D-
26 arabinose (5) was isolated in 64% yield. Of note was that D-
27 glucono-1,5-lactone (4) with its multiple hydroxy groups
28 unprotected was successfully transformed to D-arabinose (5)
48 degraded under the present reaction conditions. It is even
49 more challenging to subject unprotected disaccharides
50 possessing a glycosidic bond to chemical transformation.
51 Next, we examined disaccharrides 11 and 13 (Scheme 3).
52 Lactobionic acid (11) was converted to 3-O-β-
53 galactopyranosyl-D-arabinose (12) with the glycosidic bond
54 unaffected, albeit in low yield. Maltobionic acid (13) was
55 also shortened to 3-O--glucopyranosyl-D-arabinose (14) in
56 26% yield.
29 in a straightforward way.
Furthermore, the reaction
30 conditions tolerated the use of water as the co-solvent,
31 which is necessary for direct derivatizations of unprotected
32 sugars.
33
Other aldonolactones were subjected to the photo-
34 degradation reaction. D-Arabinose (5) was obtained also
35 from D-mannono-1,4-lactone (6) in 41% yield. D-Gulono-
36 1,4-lactone (7) afforded L-xylose (8) in 62% yield. The
37 reaction of D-galactono-1,5-lactone (9) produced D-lyxose
38 (10), which is hardly obtained from nature.
39
40 Table 3. Substrate scope with respect to monosaccharides.a
57
58 Scheme 3. Degradation of disaccharides.
59
60
It was also possible to carry out the present
41
61 degradation reaction under atomospheric oxygen (Scheme
62 4). A solution of the lactone 4, the photocatalyst 2, and
entry aldonolactone
pentose
yieldb

3
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69
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1
2
3
LiOH was placed simply in an open flask and irradiated
with blue LEDs for 18 h. D-Arabinose (5) was produced in
51% yield.
4
5
4
5
Scheme 4. Degradation of D-glucono-1,5-lactone (4) in the air
6
C. Kingston, M. D. Palkowitz, Y. Takahira, J. C. Vantourout, B.
K. Peters, Y. Kawamata, P. S. Baran, Acc. Chem. Res. 2020, 53,
72.
6
7
8
9
The polyhydroxy ketone 16 is a versatile chiral
compound often employed in asymmetric syntheses of
various natural products and bioactive compounds.16 It is
conventionally prepared from readily available quinic acid
7
8
For the environmental friendliness of photoredox catalysis, see:
G. E. M. Crisenza, P. Melchiorre, Nat. Commun. 2020, 11, 803.
Oxidative decarboxylation reactions of -hydroxycarboxylic
acids using other photomediators: a) K. Okada, K. Okubo, M.
Oda, J. Photochem. Phorobiol. A: Chem., 1991, 57, 265. b) M. H.
Habibi, S. Farhadi, J. Chem. Research (S), 1998, 776. c) H.
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10 (15) by an oxidation reaction which uses a stoichiometric
11 amount of sodium periodate17 or a hypochlorite solution.18
12 We next tried to apply the present degradation reaction to
13 the synthesis of the ketone 16 from quinic acid (15)
14 (Scheme 5). When 15 in acetonitrile/water was irradiated
15 with blue light under an oxygen atmosphere in the presence
16 of the acridinium catalyst 2 and KOH, the corresponding
17 ketone 16 was produced in 90% yield. Thus, the present
18 degradation reaction presents a facile access to the valued
19 carbonyl compound from the naturally occurring compound
20 dispensing with the use of strong oxidants or protective
21 groups.
9
70 10 The aldehyde
3 was scarcely produced under a nitrogen
71
atmosphere.
72 11 a) K. Suga, K. Ohkubo, S. Fukuzumi J. Phys. Chem. A 2006, 110,
73
74
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Fukuzumi, Chem. Commun. 2010, 46, 601.
79 14 Generation of hydrogen peroxide was confirmed by colorimetry
of the crude reaction mixture using the MQuant® test strip.
81 15 Y. Masuda, H. Tsuda, M. Murakami, Angew. Chem., Int. Ed.
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83 16 a) M. T. Barros, C. D. Maycock, M. R. Ventura, J. Org. Chem.
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23
24 Scheme 5. Degradation of quinic acid (15)
25
26
In summary, we have developed the degradation
27 reaction of aldohexonic acids which are shortened by one-
28 carbon to aldopentoses. It makes use of readily available
29 naturally occurring hexose derivatives as the feedstocks, and
30 light and molecular oxygen as the driving forces for their
31 direct transformation.
95 17 L. Malaprade, Bull. Soc. Chim. Fr. 1928, 43, 683.
96 18 N. Ran, D. R. Knop, K. M. Draths, J. W. Frost, J. Am. Chem. Soc.
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32
33
This work was supported by JSPS KAKENHI Grant
34 Numbers 15H05756 (M.M.) and 19K15562 (Y.M.).
35
36
Supporting
Information
is
available
on
37 http://dx.doi.org/10.1246/cl.******.
38 References and Notes
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