Stereospecific synthesis of (-)-neplanocin F

Article abstract of DOI:10.1080/15257770701521284

The stereospecific synthesis of (-)-neplanocin F was achieved in 15 steps from 2,3-O-isopropylidene-D-1,4-ribonolactone. The synthetic methodology can give an access through appropriate modifications to new series of carbanucleosides. Copyright Taylor & F

Full text of DOI:10.1080/15257770701521284

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Stereospecific Synthesis of (-)-
Neplanocin F
Sergio Rodriguez Ropero a , Dolorès Edmont a , Christophe Mathé a &
Christian Périgaud a
a UMR 5625 CNRS-UM II, Université Montpellier II , Montpellier,
France
Published online: 10 Dec 2007.
To cite this article: Sergio Rodriguez Ropero , Dolorès Edmont , Christophe Mathé & Christian
Périgaud (2007) Stereospecific Synthesis of (-)-Neplanocin F, Nucleosides, Nucleotides and Nucleic
Acids, 26:8-9, 1111-1114, DOI: 10.1080/15257770701521284
To link to this article: http://dx.doi.org/10.1080/15257770701521284
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Nucleosides, Nucleotides, and Nucleic Acids, 26:1111–1114, 2007
Copyright ꢀ Taylor & Francis Group, LLC
C
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770701521284
STEREOSPECIFIC SYNTHESIS OF (−)-NEPLANOCIN F
Sergio Rodriguez Ropero, Dolore`s Edmont, Christophe Mathe´,
and Christian Pe´rigaud
UMR 5625 CNRS-UM II, Universite´ Montpellier II,
2
Montpellier, France
The stereospecific synthesis of (−)-neplanocin F was achieved in 15 steps from 2,3-O-
2
isopropylidene-D-1,4-ribonolactone. The synthetic methodology can give an access through appro-
priate modifications to new series of carbanucleosides.
Keywords Neplanocin; carbanucleoside; stereospecific synthesis
INTRODUCTION
The neplanocin derivatives are an important class of naturally occurring
carbanucleosides isolated from Ampullariella regularis.[1] The neplanocin
family includes five distinct components such as (−)-neplanocin A, (−)-
neplanocin B, (−)-neplanocin C, (−)-neplanocin D, and (−)-neplanocin F
(Figure 1).
Among them, (−)-neplanocin A has received great attention due to its
interesting biological properties[2] and numerous syntheses of neplanocin
A as well as of its analogues have been reported.[3] Conversely, only two
syntheses of neplanocin F, a minor component of the neplanocin family,
have been reported including the total synthesis as a racemate of (+/−)-
neplanocin F[4] as well as the enantioselective synthesis of its unnatural (+)
enantiomer.[5] Although (−)-neplanocin F does not present antiviral activ-
ity, the stereospecific synthesis of such a carbanucleoside which is an allylic
rearranged isomer of (−)-neplanocin A, can give an access, through appro-
priate chemical modifications, to new series of carbanucleosides.
S.R.R. and D.E. are particularly grateful to The Ministerio de Educion y Ciencia, (Spain) and
Sidaction (France), respectively, for postdoctoral fellowships.
Address correspondence to Christophe Mathe´, UMR 5625 CNRS-UM II, Case courier 008, place E,
Bataillon, Universite´ Montpellier II, 34095 Montpellier Cedex, France. E-mail: cmathe@univ-montp2.fr
1111

1112
S. Rodriguez Ropero et al.
FIGURE 1 Naturally occurring carbocyclic nucleosides from the neplanocin family.
SYNTHESIS
The synthesis of (−)-neplanocin F was stereospecificaly achieved from
the known cyclopentenone 1 (Scheme 1) which was obtained from com-
mercially available 2,3-O-isopropylidene-D-1,4-ribonolactone according to
literature protocols.[6] Briefly, treatment of 1 with [(benzyloxy)methyl]
(tributyl)stannane[7] in the presence of n-BuLi in THF at −78◦C yielded
stereoselectively the 1,2-addition product which upon benzoylation pro-
vided compound 2.
Palladium-catalyzed rearrangement of 2 gave the corresponding iso-
meric allylic benzoate 3 with good yield. Saponification of 3 and protec-
tion of the resulting alcohol with benzyl group afforded cyclopentenol 4.
After acetonide cleavage, regioselective protection of the allylic hydroxyl
position[5] on compound 5 with a methoxymethyl (MOM) protecting group
led to intermediate 6 with the homoallylic secondary alcohol free at the re-
quired position. Introduction of the heterocyclic base was achieved via the
preparation of the triflate 7, which upon reaction with adenine, potassium
carbonate and a catalytic amount of 18-crown-6 ether in DMF gave solely
the N-9 alkylated product. The N-9 alkylated position was unambigously es-
tablished by NMR and UV spectra. Removal of the MOM group by treat-
ment with TFA/CH2Cl2 and well as the two benzyl ethers by treatment with
1
BCl3/CH2Cl2 at −78◦ provided the target molecule (−)-neplanocin F. H
NMR spectrum was identical with that previously reported for the unnatural
enantiomer[5] and the optical rotation agreed with literature data.[8]

1113

1114
CONCLUSION
S. Rodriguez Ropero et al.
The efficient stereospecific synthesis of (−)-neplanocin F was realized
from 2,3-O-isopropylidene-D-1,4-ribonolactone in 15 steps. The synthetic
methodology can give an access, through appropriate functionalizations to
new series of carbanucleosides.
REFERENCES
1. Hayashi, M.; Yaginuma, S.; Muto, N.; Tsujino, M. Structures of neplanocins, new antitumor antibi-
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2. De Clercq, E. Antiviral and antimetabolic activities of neplanocins. Antimicrob. Agents Chemother. 1985,
28, 84–89.
3. For recent references, see: a) Ono, M.; Nishimura, K.; Tsubouchi, H.; Nagaoka, Y.; Tomioka, K.
Total Synthesis of (−)-Neplanocin A by Using Lithium Thiolate-Initiated Michael-Aldol Tandem Cy-
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K.M.; Lee, S.K.; Kim, H.O.; Chun, M.W.; Jeong, L.S. Synthesis of 5ꢁ-substituted fluoro-neplanocin
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S-adenosylhomocysteine hydrolase. Bioorg. Med. Chem. Lett. 2004, 14, 5641–5644.
4. Bodenteich, M.; Marquez, V.E.; Hallows, W.H.; Goldstein, B.M. Synthesis and structural determina-
tion of (.+−.)-neplanocin F. J. Org. Chem. 1992, 57, 2071–2076.
5. Comin, M.J.; Leitofuter, J.; Rodr´ıguez, J.B. Enantioselective synthesis of (+)-neplanocin F. Tetrahedron
2002, 58, 3129–3136.