Journal of the American Chemical Society
Communication
Notes
Table 3. Synthesis of C(2)-Fluorinated Pentoses from
Lactones
ab c
, ,
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Financial support was provided by NIHGMS (R01 GM103558-
01) and gifts from Merck, AbbVie, and Amgen. We would like to
thank Dr. Zoe R. Turner for X-ray crystallographic data.
REFERENCES
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(1) Nelson, D. L.; Cox, M. M. Lehninger Principles of Biochemistry, 5th
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a
b
Intermediate fluorinated lactones 31a−33a not depicted. All lactols
c
recovered as anomeric mixtures. Diastereomeric ratios determined
by 1H NMR analysis of isolated material. Relative stereochemistry
determined by NOESY.
(4) For a general review of the de novo synthesis of monosaccharides:
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Scheme 1. Enantioselective Route to Gemcitabine and
PSI-6130
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(14) Reactions with prochiral silyl ketene acetals generally provide with
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diastereomer after isolation. Cleavage of the OTMP group under
reducing conditions followed by treatment with acid promoted
cyclization to form lactone 37. We were pleased to find that
the lactone was obtained as a crystalline solid and that its
enantiopurity could be increased to 99% ee after recrystalliza-
tion.22 Further elaboration of 37 delivered PSI-6130 in 25% yield
and seven total steps from α,β-dioxyaldehyde 1.
(16) In some cases, the product mixture also contained the open-chain
aryl ketone, which was competent in the reduction step.
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avoid β-elimination during enolization.
(20) (a) Chou, T. S.; Heath, P. C.; Patterson, L. E.; Poteet, L. M.;
Lakin, R. E.; Hunt, A. H. Synthesis 1992, 565. (b) Chang, Y. K.; Lee, J.;
Park, G.-S.; Lee, M.; Park, C. H.; Kim, H. K.; Lee, G.; Lee, B.-Y.; Baek, J.
Y.; Kim, K. S. Tetrahedron 2010, 66, 5687.
ASSOCIATED CONTENT
* Supporting Information
Experimental details and crystallographic data. This material is
■
S
AUTHOR INFORMATION
Corresponding Author
■
(21) Wang, P.; Chun, B.-K.; Rachakonda, S.; Du, J.; Zhan, N.; Shi, J.;
Stec, W.; Cleary, D.; Ross, B. S.; Sofia, M. J. J. Org. Chem. 2009, 74, 6819.
(22) Absolute stereochemistry of 37 was confirmed by X-ray
crystallography (data in SI).
Author Contributions
†These authors contributed equally.
5903
dx.doi.org/10.1021/ja502205q | J. Am. Chem. Soc. 2014, 136, 5900−5903