Fortunately, both the compounds 4a and 4b are good crystalline
solids and they were crystallized using dichloromethane-hexane
mixture to obtain crystals useful for diffraction. Single crystal
analysis using copper source clearly established their absolute
stereochemistry as depicted in Scheme 3. Following the same
reaction sequence, individual diols 4a and 4b were transformed
to (R)-ktedonoketone and (S)-ktedonoketone, respectively.
Spectral data of both compounds (R)-1 and (S)-1 were compared
with the data of natural product and it was found to be identical.
The specific rotation for naturally isolated ktedonoketone was
Supplementary data
Supplementary data (Experimental details, copies NMR
spectra, X-ray details and CIF file) associated with this article
can be found in the online version at http:xxxx.
References and notes
1
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Igarashi Y, Yamamoto K, Ueno1 C, Yamada N, Saito K, Takahashi K,
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2
3
1
observed to be [α]
D
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6
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recorded [α]
D
3
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(
ktedonoketone. The mismatched sign for specific rotation left the
absolute configuration of natural ketdonoketone unassigned by
Enomoto group.
3
.
Yabe S., Aiba Y., Sakai Y., Hazaka M., Yokota A. Int J Syst Evol
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4
.
2
7.7
In our case, the specific rotation observed for (R)-1 [α]
D
=
2
8.7
5. Ishii S., Saito K., Kuwahara S., Enomoto M. Tetrahedron Lett. 2020; 61:
51915.
+
71.00 (c 0.7, CHCl
3
) and for (S)-1 [α]
D
= -71.18 (c 1.0,
1
CHCl
3
). The both enantiomerically pure forms have opposite
6
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signs and specific rotation values clearly depict that natural
ktedonoketone has “R” configuration. Although the discrepancy
in magnitude of specific rotation has been observed when
compared with natural Ktedonoketone, but it could be pertained
that low concentration of natural Ktedonoketone (c 0.04)1 or
small impurities with high magnitude of rotations in large
amount of synthetic ktedonoketone, may deviate the magnitude
while measuring specific rotations.5 As, the rotations are in
opposite signs, we claim to have an unambiguous assignment of
natural ktedonoketone as (R)-ktedonoketone. In addition, our
present route can be utilized for the generation of library of
molecules as one can employ readily accessible various amino
acids and Grignard reagents (Scheme 4).
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O
O
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OH
*
OH
NH2
readily avaible
amino acids
compound library based
on ktedenoketone scaffold
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1
1
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5. There are a few methods available in the literature to improve the
daisetereoselectivity, including chiral reagents. For example, when we
tried the reaction with allylbromide in presence of Indium metal11 the
diastereoselectivity was improved to 8:2 ratio. As our goal is to fix
stereochemistry and access to both enantiomers of the target natural
product, we did not put additional efforts.
Scheme 4. Plan to access ktedonoketone-based library
In summary, we have accomplished the synthesis of both the
enantiomers (R)-ktedonoketone and (S)-ktedonoketone. Wacker
oxidation and aldol reactions are the key steps in present
synthesis of ktedonoketone. Our developed synthetic route is
amenable to access large number of compounds based on target
skeleton.
Acknowledgments
DSR and MD thanks Department of Biotechnology (DBT),
New Delhi for the funding ([BT/PR23544/MED/30/1858/2017).
RC thanks UGC for fellowship. GRK thanks DST-SERB for
Ramanujan fellowship.