Abstract
A versatile and efficient route to both enantiomers of 4′-quaternary 2′-deoxy-3′-
and -4′-epi-β-C- and -N-nucleosides is described. The asymmetric synthesis involves the SAMP/RAMP-hydrazone
α-alkylation methodology and diastereoselective nucleophilic 1,2-additions. Manipulation
of the substituents in the anomeric position leads to the thermodynamically more stable
β-anomers of excellent diastereo- and enantiomeric purity (>99% de and ee).
Key words
nucleoside analogues - asymmetric synthesis - hydrazones - quaternary stereocentres
- diastereoselective reduction
References
<A NAME="RZ04408SS-1A">1a</A>
Nomura M.
Shuto S.
Tanaka M.
Sasaki T.
Mori S.
Shigeta S.
Matsuda A.
J. Med. Chem.
1999,
42:
2901
<A NAME="RZ04408SS-1B">1b</A>
Shuto S.
Kanazaki M.
Ichikawa S.
Minakawa N.
Matsuda A.
J. Org. Chem.
1998,
63:
746
<A NAME="RZ04408SS-1C">1c</A>
Waga T.
Ohuri H.
Meguro H.
Nucleosides Nucleotides
1996,
15:
287
<A NAME="RZ04408SS-1D">1d</A>
O-Yang C.
Wu HY.
Fraser-Smith EB.
Walker KAM.
Tetrahedron Lett.
1992,
33:
37
<A NAME="RZ04408SS-1E">1e</A>
O-Yang C.
Kurz W.
Eugui EM.
McRoberts MJ.
Verheyden JPH.
Kurz LJ.
Walker KAM.
Tetrahedron Lett.
1992,
33:
41
<A NAME="RZ04408SS-1F">1f</A>
Rangam G.
Rudinger NZ.
Müller HM.
Marx A.
Synthesis
2005,
1467
<A NAME="RZ04408SS-1G">1g</A>
Kohgo S.
Yamada K.
Kitano K.
Iwai Y.
Sakata S.
Ashida N.
Hayakawa H.
Nameki D.
Kodama E.
Matsuoka M.
Mitsuya H.
Ohrui H.
Nucleosides, Nucleotides Nucleic Acids
2004,
23:
671
<A NAME="RZ04408SS-2">2</A>
Marx A.
Summerer D.
Synlett
2004,
217
<A NAME="RZ04408SS-3">3</A>
Kool ET.
Annu. Rev. Biochem.
2002,
71:
191
For an overview, see:
<A NAME="RZ04408SS-4A">4a</A>
Perspectives in Nucleoside and Nucleic Acid Chemistry
Kisakürek MV.
Rosemeyer H.
VHCA;
Zürich:
2000.
For a review on aza nucleosides, see:
<A NAME="RZ04408SS-4B">4b</A>
Yokoyama M.
Momotake A.
Synthesis
1999,
1541
For a review on thio nucleosides, see:
<A NAME="RZ04408SS-4C">4c</A>
Yokoyama M.
Synthesis
2000,
1637
<A NAME="RZ04408SS-4D">4d</A>
Alho MAM.
Errea MI.
Sguerra VL.
D’Accorso NB.
Talarico LB.
Garcia CC.
Damonte EB.
J. Heterocycl. Chem.
2005,
42:
979
<A NAME="RZ04408SS-5">5</A>
Vorbrüggen H.
Ruh-Pohlenz C.
Org. React.
2000,
55:
1
<A NAME="RZ04408SS-6">6</A>
Brotschi C.
Häberli A.
Leumann CJ.
Angew. Chem. Int. Ed.
2001,
40:
3012 ; Angew. Chem. 2001, 113, 3101
<A NAME="RZ04408SS-7">7</A> For a review on C-nucleosides, see:
Wu Q.
Simons C.
Synthesis
2004,
1533
<A NAME="RZ04408SS-8">8</A>
Hess MT.
Schwitter U.
Petretta M.
Giese B.
Naegli H.
Biochemistry
1997,
36:
2332
<A NAME="RZ04408SS-9">9</A>
Enders D.
Hieronymi A.
Ridder A.
Synlett
2005,
2391
<A NAME="RZ04408SS-10">10</A> For a review, see:
Enders D.
Voith M.
Lenzen A.
Angew. Chem. Int. Ed.
2005,
44:
1304
For reviews, see:
<A NAME="RZ04408SS-11A">11a</A>
Job A.
Janeck CF.
Bettray W.
Peters R.
Enders D.
Tetrahedron
2002,
58:
2253
On hydrazone cleavage, see:
<A NAME="RZ04408SS-11B">11b</A>
Enders D.
Wortmann L.
Peters R.
Acc. Chem. Res.
2000,
33:
157
<A NAME="RZ04408SS-12">12</A>
CCDC 617802 contains the supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.
<A NAME="RZ04408SS-13">13</A>
Imamoto T.
Tawarayama Y.
Sugiura Y.
Mita T.
Hatanaka Y.
Yokoyama M.
J. Org. Chem.
1984,
49:
3904
<A NAME="RZ04408SS-14">14</A>
Evans DA.
Chapman KT.
Carreira EM.
J. Am. Chem. Soc.
1988,
110:
3560
<A NAME="RZ04408SS-15A">15a</A>
Sugimura H.
Osumi K.
Yamazaki T.
Yamaya T.
Tetrahedron Lett.
1991,
32:
1813
<A NAME="RZ04408SS-15B">15b</A>
Sujino K.
Sugimura H.
Synlett
1992,
553
<A NAME="RZ04408SS-15C">15c</A>
Nicolaou KC.
Seitz SP.
Papahatjis DP.
J. Am. Chem. Soc.
1983,
105:
2430
<A NAME="RZ04408SS-16">16</A>
Enders D.
Breuer I.
Drosdow E.
Synthesis
2005,
3239
