Enantioselective reduction of 2-ketoalkanephosphonate by baker's yeast

Article abstract of DOI:10.1080/10426500212307

Bioreduction of 2-oxo-3-halo (or azido) alkanephosphonates and 4-ethoxy-4,2-dioxobutanephosphonates by baker's yeast afforded 3-substituted 2-hydroxyalkanephosphonates in moderate to good yields and ee value. Moreover, a regio- and stereoselective bioreduction of 2,3-dioxoalkanephosphonates and 2,4-dioxoalkanephosphonates by baker's yeast was studied also. The resulting chiral hydroxy compounds can be used as chirons for the stereoselective synthesis of biologically active molecules.

Full text of DOI:10.1080/10426500212307

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Phosphorus, Sulfur, and Silicon and the Related
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Enantioselective Reduction of 2-
Ketoalkanephosphonate by Baker's Yeast
Ke Wang a , Zuyi Li a & Chengye Yuan a
a Shanghai Institute of Organic Chemistry , Chinese Academy of Sciences , Shanghai, China
Published online: 27 Oct 2010.
To cite this article: Ke Wang , Zuyi Li & Chengye Yuan (2002) Enantioselective Reduction of 2-Ketoalkanephosphonate by
Baker's Yeast, Phosphorus, Sulfur, and Silicon and the Related Elements, 177:6-7, 1797-1800, DOI: 10.1080/10426500212307
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:1797–1800
C
Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290092857
ENANTIOSELECTIVE REDUCTION OF
2-KETOALKANEPHOSPHONATE BY BAKER’S YEAST
Ke Wang, Zuyi Li, and Chengye Yuan
Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, Shanghai, China
(Received July 29, 2001; accepted December 25, 2001)
Bioreduction of 2-oxo-3-halo (or azido) alkanephosphonates and
4-ethoxy-4,2-dioxobutanephosphonates by baker’s yeast afforded
3-substituted 2-hydroxyalkanephosphonates in moderate to good yields
and ee value. Moreover, a regio- and stereoselective bioreduction of
2,3-dioxoalkanephosphonates and 2,4-dioxoalkanephosphonates by
baker’s yeast was studied also. The resulting chiral hydroxy compounds
can be used as chirons for the stereoselective synthesis of biologically
active molecules.
Keywords: Baker’s yeast; dicarbonyl phosphonates; monocarbonyl
phosphonates
Baker’s yeast (Saccharomyces cerevisiae) is now well recognized as
a valuable stereoselective reagent in biotransformations of organic
3
molecules.1 The asymmetric reduction of carbonyl groups with this
microbiological substance has been studied extensively; neverthe-
less, there are only a few reports dealing with the enzymatic reduc-
tion of their phosphorus analogs, namely, -ketoalkanephosphonates.4
On the other hand, chiral hydroxyalkanephosphonic acids have re-
ceived much attention due to their unique physiological activities.
As a part of our systematic study on the biotransformation of
organicphosphorus compounds, we report in this paper the biore-
ductive behaviors of monocarbonyl phosphonates and dicarbonyl
phosphonates.
This project was supported by the National Natural Science Foundation of China
(NNSFC), grants 20072052 and 29832050.
Address correspondence to Chengye Yuan, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China.
1797

1798
K. Wang et al.
FIGURE 1
RESULTS AND DISCUSSION
Reduction of Monocarbonyl Phosphonates
Bioreduction of 3-substituted 2-oxoalkanephosphonates by baker’s
yeast (Figure 1 and Table I) afforded 3-substituted 2-hydroxy-
alkanephosphonates in moderate to good yields and ee value. These
compounds could serve as useful chirons for the stereoselective syn-
thesis of phosphorus analogs of biologically active molecules, including
(R)-carnitine and (R)-GABOB.
Reduction of Dicarbonyl Phosphonates
The reduction of 4-alkoxy-4,2-dioxobutanephosphonate is shown in
Figure 2.
2-Ketoalkanephosphonates are commonly employed as synthetic
reagents, particularly in the Horner–Wadsworth–Emmons reaction.
The nonracemic 3(4)-hydroxy-2-oxo-alkanephosphonates should be im-
portant as synthetic building blocks, since they are phosphorus-
functionalized aldols. The Horner–Emmons olefination leading to
nonracemic 1-hydroxy-4-alken-3-ones is therefore attractive. An
TABLE I Reduction of 1 with Baker’s Yeast
Substrate
R
X
Time (h)
Yield (%) ee (%)a
Configurationb
1a
1b
1c
1d
1e
1f
1g
1h
1i
Me
Et
iPr
nBu
Et
iPr
nBu
Et
CH2Cl
CH2Cl
CH2Cl
CH2Cl
CH2Br
CH2Br
CH2Br
CH2N3
CF3
24
12
24
24
24
24
24
12
48
24
74
82
57
88
35c
41c
55c
77
86
55
70
72
13
70
83
52
87
92
52
20
R
R
—
R
R
—
R
S
—
—
Et
Et
1j
C3F7
aThe ee (%) was determined by the use of quinine as a chiral solvating agent.
bThe absolute configuration was determined according to Mosher’s methods.
cThe 2-oxo-propane-phosphonate was isolated as a by-product.

Enantioselective Bioreduction
1799
FIGURE 2 R1 = Me, Et, i-Pr, n-Bu; R2 = Me; yield 46–77%, ee 55–85%.
interesting route to
a nonracemic 3(or 4)-hydroxy-2-ketophos-
phonate has been developed by bioreduction of dialkyl 2,3(or 4)-
dioxoalkanephosphonates.
Regio- and Stereoselective Reduction of Dialkyl
2,3-Dioxoalkanephosphonates
-Hydroxyketones are versatile chiral synthons for the construction
of optical active organic compounds due to reactive functional groups:
carbonyl and hydroxyl groups, which can easily be transformed to vici-
nal diols, amino ketones, and other functional groups. To obtain chiral
-hydroxyketones, reduction mediated by yeast is a powerful tool. In
yeast reduction, two regioisomeric -hydroxyketones are produced, and
these hydroxyketones can be successively reduced to the diol. There-
fore, chemical yields of the -hydroxyketones are low. For asymmetric
synthesis in such a reduction process, chemoselectivity, regioselectivity,
and enantioselectivity should be taken in consideration (Figure 3).
Regio- and Stereoselective Reduction of Dialkyl
2,4-Dioxoalkanephosphonates
A series of phosphorus-based carbonyl compounds, namely, dialkyl 2,4-
dioxoalkanephosphonates (8), was prepared by reaction of carbanion
FIGURE 3
FIGURE 4 R1 = Et, n-Bu; R2 = Me, CF3, C3H7; (1) baker’s yeast; (2) yield
9/10 = 45/24 or 67%, ee 9 90–94%.

1800
K. Wang et al.
FIGURE 5 X = H, p-MeO, p-Me, p-Cl, p-Br, p-F, m-NO2; (1) DBU, LiCl, 12–
24 h, rt; (2) yield 53–72%.
FIGURE 6 X = H, Me, MeO; (1) baker’s yeast.
resulted from 2-methyl-2-oxoethanephosphonate with substituted ac-
etates. Bioreduction of 8 by baker’s yeast at 30 C for 24–48 h offered
an isomeric mixture consisting of 9/10, when R1 is methyl, in 45/24%
yield as well as 92/80% ee value, respectively. It is interesting to note
that when R2 is CF3 or C3F7, a regio- and stereoselective reduction
was observed. Only 9 was obtained, in 54–67% yield and 90–94% ee
value.
The chiral 4-hydroxy-2-oxoalkylphosphonates 9 thus obtained
underwent Horner–Emmons olefination as expected. Thus a se-
ries of trans-6,6,6-trifluoro-5-hydroxy-1-(substituted)phenyl-1-hexen-
3-ones 12 was prepared by reaction of 5,5,5-trifluoro-4-hydroxy-2-
oxopentanephosphonates with substituted benzaldehyde under very
mild condition in 33–67% yields (Figure 5).
It is interest to note that under the Horner–Wadsworth–Emmons
reaction, compound 6 gave 13 conveniently and that provided
14, a chiral vicinal diol, upon another baker’s yeast reduction
(Figure 6).
REFERENCES
[1] R. Csuk and B. I. Glanzer, Chem. Rev., 91, 49 (1991).
[2] R. Csuk and B. I. Glanzer, In Stereoselective Biocatalysis, ed. R. N. Patel (Marcel
Dekker, New York, 2000), p. 527.
[3] S. Servi, Synthesis, 8, 1 (1990).
[4] E. Zymanczyk-Duda and B. Lejczak, Tetrahedron, 51, 11809.