Synthesis of Carbovir and Abacavir from UNIT 14.

4
a Carbocyclic Precursor
A facile method for the production of carbocyclic nucleosides from the versatile lactam
2-azabicyclo[2.2.1]hept-5-en-3-one was originated in the authors’ laboratory (Vince and
Daluge, 1978). The lactam, subsequently coined the Vince lactam by Chemical and
Engineering News (Stinson, 1994; Rouhi, 2003), is now commercially available either
as a racemic mixture or as enantiomers. Following the identification of a retrovirus
(human immunodeficiency virus or HIV) as the etiological agent of human acquired
immunodeficiency syndrome (AIDS), an intense effort was made to identify drugs for
the treatment of this disease. The lactam method was employed in the synthesis of a new
class of anti-HIV nucleosides. These carbocyclic 2
,3
-didehydro-2
,3
-dideoxy-2-amino-
6-substituted purines were termed carbovirs (Vince et al., 1988; Vince and Hua, 1990).
The parent compound, carbocyclic 2
,3
-didehydro-2
,3
-dideoxyguanosine (carbovir), is
enzymatically converted to the active form, carbovir triphosphate, which inhibits HIV
reverse transcriptase. All other active derivatives in this series are ultimately converted to
the same active metabolite. The anti-HIV drug derived from this series, abacavir (Ziagen),
obtains its activity via conversion to carbovir triphosphate. The preparation of the key
intermediate, cis-[4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopentenyl]carbinol, is de-
scribed for the preparation of carbovir and abacavir.

PREPARATION OF CARBOVIR AND ITS 6-CHLOROPURINE PRECURSOR BASIC

PROTOCOL 1
The synthetic procedure for the synthesis of carbovir and abacavir via the 6-chloropurine
intermediate is outlined in Figure 14.4.1. The protocol described here includes the entire
procedure from the starting Vince lactam to carbovir, and is based on the method using
the racemic lactam. The individual enantiomers can be used in the same reactions to
obtain the optical isomers. The starting lactam can be made by the procedure described
by Vince and Daluge (1978) or can be obtained commercially from a supplier such as
Sigma-Aldrich. The final step from the 6-chloropurine precursor (S.6) to carbovir (S.7) is
presented as two different methods that depend on the desired synthesis scale. Synthesis
of abacavir (S.8) from S.6 is described in Basic Protocol 2.

Materials
2-Azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam; Sigma-Aldrich)
12 N HCl
1 N dry HCl/methanol
Pyridine
Acetic anhydride
Ethyl acetate
Anhydrous calcium chloride
Sodium borohydride
Tetrahydrofuran (THF)
Barium hydroxide
Dry ice
Absolute ethanol
1-Butanol
2-Amino-4,6-dichloropyrimidine (Aldrich)
Triethylamine
Silica gel 60 (230 to 400 mesh; EM Science)
Chloroform (CHCl3 ) Biologically
Active
Nucleosides
Contributed by Robert Vince and Mei Hua 14.4.1
Current Protocols in Nucleic Acid Chemistry (2006) 14.4.1-14.4.8
Copyright 
C 2006 by John Wiley & Sons, Inc.
Supplement 25
 Methanol (MeOH)
p-Chloroaniline
Ice-salt bath
Sodium nitrite
Acetic acid
Sodium acetate trihydrate
Acetone
Zinc dust
Nitrogen source
Diethyl ether
Triethyl orthoformate
3 N NaOH
Reflux condenser
Mechanical stirrer
Rotary evaporator
Büchner filter funnel
Silicon oil bath
5.0 × 15–, 2.0 × 18–, 4.0 × 10–, 2.0 × 7.5–, and 5 × 5–cm columns
Silica gel 60 F254 TLC plates (0.25-mm layer; EM Science)
Additional reagents and equipment for column chromatography (APPENDIX 3E) and
TLC (APPENDIX 3D)

Prepare cis-acetamidocyclopent-2-enemethyl acetate (S.1)

1. Dissolve 50 g Vince lactam in 750 mL of 1 N HCl and reflux for 1 hr (120◦ C).
Concentrate solution to dryness on a rotary evaporator to obtain the carboxylic
acid–amine salt (66 g; 88% yield).
2. Dissolve the carboxylic acid–amine salt in 750 mL of 1 N dry HCl/methanol and
reflux for 1 hr (75◦ C). Remove the volatile material on a rotary evaporator to obtain
the methyl ester–amine salt as a syrup.
To prepare 1 N dry HCl/methanol, pass dry HCl gas into MeOH, under cooling, then
adjust to a 1 N concentration.

3. Dissolve the syrup in 250 mL pyridine and 200 mL acetic anhydride, and stir
overnight at room temperature.
4. Concentrate the solution on a rotary evaporator and crystallize from 200 mL ethyl
acetate to yield the ester-acetamide compound (70 g; 83% yield; m.p. 64◦ -66◦ C).
5. Prepare the reducing agent by mixing 47.7 g ground calcium chloride and 32.55 g
sodium borohydride in 900 mL THF, and stir 1 hr at room temperature.
6. Add 52.5 g of the ester-acetamide to 450 mL THF, and then add to the reducing
agent. Stir 18 hr at ambient temperature.
7. Carefully and gradually add 550 mL ice-cold water to hydrolyze the complex. First
add 3-mL portions, then gradually increase the portion size added.
8. Acidify the cold mixture to pH 1.5 by adding 6 N HCl.
9. Remove the solvent on a rotary evaporator, dissolve the residue in 370 mL pyridine
and 370 mL acetic anhydride, and stir overnight at ambient temperature.
Synthesis of 10. Concentrate the solution to dryness on a rotary evaporator and collect the pure
Carbovir and
Abacavir from a product (S.1) by crystallization from 250 mL ethyl acetate overnight. On the next
Carbocyclic day, filter the product.
Precursor
cis-Acetamidocyclopent-2-enemethyl acetate (S.1): 41 g (73%). m.p. 65◦ C.
14.4.2
Supplement 25 Current Protocols in Nucleic Acid Chemistry
Figure 14.4.1 Preparation of abacavir and carbovir from a common 6-chloropurine precursor
that is derived from Vince lactam.

Remove acetyl groups

11. Prepare a 0.5 N solution of barium hydroxide in 400 mL water.
12. Add 10.0 g (50 mmol ) S.1 to the barium hydroxide solution and reflux the mixture
overnight (110◦ C).
13. Cool the mixture to room temperature. Neutralize the solution to pH 7 by adding
dry ice with stirring.
14. Remove the precipitate through a Büchner filter funnel.
Biologically
15. Concentrate the filtrate to dryness on a rotary evaporator. Active
Nucleosides
16. Extract the residue three times with 150 mL absolute ethanol.
14.4.3
Current Protocols in Nucleic Acid Chemistry Supplement 25
 17. Concentrate the ethanol extract on a rotary evaporator to a colorless syrup of crude
S.2.
(±)-cis-(4-Aminocyclopent-2-enyl)methanol (S.2) is used directly for the next step with-
out purification.

Perform pyrimidine heterocycle substitution

18. Dissolve S.2 in 200 mL of 1-butanol.
19. Add 12.3 g (75 mmol) 2-amino-4,6-dichloropyrimidine and 30 mL triethylamine to
the 1-butanol solution and reflux the mixture on a silicon oil bath for 48 hr (130◦ C).
20. Remove the volatile materials on a rotary evaporator, <40◦ C, to yield a syrup.
21. Adsorb the syrup onto 30 g silica gel. Pack the silica gel sample onto a 5.0 × 15–cm
column (APPENDIX 3E).
22. Elute the column three times with 300 mL each of 40:1, 30:1, and 20:1 (v/v)
CHCl3 /MeOH, and check each fraction by TLC (APPENDIX 3D) using 10:1 (v/v)
CHCl3 /MeOH (Rf = 0.31).
The desired fractions are eluted with the 20:1 CHCl3 /MeOH fractions.

23. Collect product fractions and concentrate them on a rotary evaporator to obtain a
thick syrup.
24. Crystallize the syrup from 150 mL ethyl acetate to yield white crystals.
(±)-cis-[4-(2-Amino-6-chloropyrimidin-4-ylamino)cyclopent-2-enyl]methanol (S.3):
9.15 g (76%). m.p. 132◦ −134◦ C.

Derivatize 5 position of pyrimidine ring

25. Dissolve 1.47 g (11.5 mmol) p-chloroaniline in 25 mL of 3 N HCl and cool on an
ice-salt bath.
26. Dissolve 870 mg (12.5 mmol) sodium nitrite in 10 mL water and cool on an ice-salt
bath.
27. Add the cold sodium nitrite solution to the cold p-chloroaniline solution to form a
cold diazonium salt solution.
28. Dissolve 2.40 g (10 mmol) S.3 into 50 mL water, 50 mL acetic acid, and 20 g
sodium acetate trihydrate.
29. Add the cold diazonium salt solution to the S.3 solution and stir the mixture
overnight at ambient temperature.
30. Remove the yellow precipitate by filtering with a Büchner funnel under vacuum,
and wash the precipitate with 200 mL cold water to pH 7 (check with pH paper).
31. Air dry the solid in a well-ventilated chemical fume hood.
32. Collect the dried product (S.4).
Crude (S.4): 3.60 g (94%). m.p. 229◦ C (dec).

33. Purify the crude product from 500 mL of 1:2 (v/v) acetone/methanol to yield a pure
sample.
(±)-cis-{4-[2-Amino-6-chloro-5-(4-chloro-phenylazo)pyridin-4-ylamino]cyclopent-2-
Synthesis of enyl}methanol (S.4): m.p. 241◦ -243◦ C (dec). MS: m/e 378 and 380 (M+ and M+ +2).
Carbovir and IR (KBr) (cm−1 ): 3600-3000, 1620, 1580. Anal. calcd. (C16 H16 Cl2 N8 O): C, 50.67; H,
Abacavir from a 4.25; N, 22.16; found: C, 50.59; H, 4.20; N, 21.99.
Carbocyclic
Precursor

14.4.4
Supplement 25 Current Protocols in Nucleic Acid Chemistry
Perform reductive cleavage of azo function
34. Mix 379 mg (1.0 mmol) S.4 with 0.65 g (10 mmol) zinc dust, 0.32 mL acetic
acid, 15 mL water, and 15 mL ethanol. Reflux the mixture under nitrogen for 3 hr
(130◦ C).
This reaction can be scaled up five to ten times. For example, use 1.89 g (5.0 mmol) S.4
with 3.25 g (50 mmol) zinc dust, 1.6 mL acetic acid, 75 mL water, and 75 mL ethanol.
Use 10 g silica gel with a 4 × 14–cm column (step 37), 200 mL of 1:1 methanol/diethyl
ether to yield pink crystal product (step 40), and the resulting yield of S.5 is 0.85 g.

35. Remove the zinc dust on a Büchner funnel.

36. Evaporate filtrate to a thick syrup on a rotary evaporator with a water aspirator.
37. Adsorb the syrup onto 2 g silica gel. Pack the sample onto a 2.0 × 18–cm column.
38. Elute the column with 15:1 (v/v) CHCl3 /MeOH and check each fraction by TLC
using 10:1 (v/v) CHCl3 /MeOH (Rf = 0.35).
39. Collect product fractions and concentrate to a pink syrup on a rotary evaporator
with a water aspirator.
40. Purify the crude product from 40 mL of 1:1 (v/v) methanol/diethyl ether to yield a
pink crystal product.
(±)-cis-[4-(2,5-Diamino-6-chloro-pyrimidin-4-ylamino)cyclopent-2-enyl]methanol
(S.5): 170 mg (66%). m.p. 168◦ -170◦ C. MS: m/e 255 and 257 (M+ and M+ +2). IR
(KBr) (cm−1 ): 3600-3000, 1620, 1580. Anal. calcd. (C10 H14 ClN5 O): C, 46.97; H, 5.52;
N, 27.39; found: C, 47.10; H, 5.56; N, 27.36.

Form purine heterocycle by ring closure

41. Mix 1.41 g (5.5 mmol) S.5, 30 mL triethyl orthoformate, and 1.40 mL of 12 N HCl.
Stir the mixture overnight at ambient temperature.
42. Concentrate the mixture to dryness on a rotary evaporator.
43. Add 40 mL of 0.5 N HCl to the residue and stir for 1 hr at room temperature.
44. Neutralize the mixture to pH 8 by adding 1 N NaOH.
45. Concentrate the mixture on a rotary evaporator.
46. Adsorb the residue on 7.5 g silica gel. Pack the sample onto a 4.0 × 10–cm column.
47. Elute the column with 20:1 (v/v) CHCl3 /MeOH and check each fraction by TLC
using 5:1 (v/v) CHCl3 /MeOH (Rf = 0.64).
48. Collect product fractions and concentrate to a white solid (S.6).
Yield: 1.18 g (80%).

49. Recrystallize the crude product from 25 mL ethanol to yield the pure 6-chloropurine
precursor.
(±)-cis-[4-(2-Amino-6-chloropurin-9-yl)cyclopent-2-enyl]methanol (S.6): m.p. 145◦ -
147◦ C. MS: m/e 265 and 267 (M+ and M+ +2). IR (KBr) (cm−1 ): 3600-2600, 1620,
1580. 1 H NMR (DMSO-d6 ): 8.01 (s, 1H, H8), 6.98-6.80 (s, 2H, NH2 ), 6.15-6.05 and
5.94-5.84 (dd, 2H, CH=CH, J = 5.0 Hz), 5.50-5.32 (m, 1H, H1), 4.79-4.60 (t, 1H,
CH2 OH), 3.51-3.39 (d, 2H, CH2 OH), 2.95-2.71 (m, 1H, H4
), 2.69-2.55 (m, 1H, CHH
),
1.72-1.50 (m, 1H, CHH
). Anal. calcd. (C11 H12 N5 OCl· 34 H2 O): C, 47.31; H, 4.87; N,
25.09; found: C, 47.40; H, 4.94; N, 25.21.
Biologically
Active
Nucleosides

14.4.5
Current Protocols in Nucleic Acid Chemistry Supplement 25
 Prepare carbovir
For a 100-mg scale

50a. Mix 266 mg (1.0 mmol) S.6 and 20 mL of 0.33 N NaOH, and reflux the mixture
for 5 hr (120◦ C).
51a. Concentrate the solution on a rotary evaporator.
52a. Adsorb the residue onto 2 g silica gel. Pack the sample onto a 2.0 × 7.5–cm column.
53a. Elute the column with 5:1 (v/v) CHCl3 /MeOH and check each fraction by TLC
using 5:1 (v/v) CHCl3 /MeOH (Rf = 0.27).
54a. Collect product fractions and concentrate to a white solid on a rotary evaporator
with a water aspirator.
55a. Recrystallize the crude product from 20 mL of 1:4 (v/v) methanol/water to yield a
white crystal product.
(±)-cis-2-Amino-9-(4-hydroxymethylcyclopent-2-enyl)-9H-purin-6-ol (carbovir; S.7):
152 mg (61%). m.p. 254◦ -256◦ C (dec). MS: m/e 247(M+ ). IR (KBr) (cm−1 ): 3600-2600,
1600. 1 H NMR (DMSO-d6 ): 10.57-10.50 (s, 1H, 6-OH), 7.60-7.56 (s, 1H, H8), 6.50-6.35
(s, 2H, NH2 ), 6.14-6.06 and 5.89-5.81 (dd, 2H, CH=CH, J = 5.0 Hz), 5.38-5.26 (m, 1H,
H1
), 4.76-4.65 (t, 1H, CH2 OH), 3.47-3.39 (d, 2H, CH2 OH), 2.92-2.80 (m, 1H, H4
),
2.65-2.55 (m, 1H, CHH
), 1.64-1.50 (m, 1H, CHH
). Anal. calcd. (C11 H13 N5 O2 · 43 H2 O):
C, 50.66; H, 5.60; N, 26.86; found: C, 50.44; H, 5.59; N, 26.76.

For a 1- to 10-g scale

50b. Dissolve 4.3 g (16 mmol) S.6 into 220 mL of 1 N HCl and 60 mL methanol. Heat
solution 9 hr on a 60◦ C silicon oil bath.
When scaled up to 5 g, some polymer was obtained (sticky in appearance). Therefore,
acidic conditions were used to avoid polymerization.

51b. Concentrate the solution on a rotary evaporator to 50 mL.

52b. Neutralize the solution to pH 7 by adding 3 N NaOH. Evaporate the solution.
53b. Adsorb the residue onto 10 g silica gel. Pack the sample onto a 5 × 5–cm column.
54b. Elute with 5:1 (v/v) CHCl3 /MeOH and check each fraction by TLC using 5:1 (v/v)
CHCl3 /MeOH (Rf = 0.27).
55b. Collect product fractions to yield crude product (S.7).
Yield: 3.1 g (77%).
56b. Recrystallize the crude product from 35 mL 1:4 (v/v) methanol/water to yield the
pure compound.
Carbovir (S.7): 2.4 g (60%). m.p. 254◦ -256◦ C (dec).

BASIC PREPARATION OF ABACAVIR FROM THE 6-CHLOROPURINE

PROTOCOL 2 PRECURSOR
The synthesis of abacavir (S.8) from the 6-chloropurine intermediate (S.6) is illustrated
in Figure 14.4.1. The scale presented is comparable to the smaller scale method in Basic
Protocol 1. This reaction could be scaled up without any modifications except for the
Synthesis of amounts of ethanol and cyclopropylamine. For example, a 10-fold scale up would require
Carbovir and
Abacavir from a a 2.5-fold increase in the amounts of ethanol and cyclopropylene.
Carbocyclic
Precursor

14.4.6
Supplement 25 Current Protocols in Nucleic Acid Chemistry
Materials
6-Chloropurine precursor (S.6; see Basic Protocol 1)
Ethanol
Cyclopropylamine
1 N NaOH
Silica gel (230 to 400 mesh; EM Science)
Chloroform (CHCl3 )
Methanol (MeOH)
Acetonitrile
Silicon oil bath
Rotary evaporator
2 × 13–cm column
Silica gel 60 F254 TLC plate (0.25-mm layer; EM Science)
Additional reagents and equipment for column chromatography (APPENDIX 3E) and
TLC (APPENDIX 3D)
1. Mix 0.26 g (1.0 mmol) S.6, 5 mL ethanol, and 20 g cyclopropylamine. Reflux the
mixture on a silicon oil bath for 25 hr (55◦ C).
2. Add 1 mL (1 mmol) of 1 N NaOH to the mixture. Concentrate the mixture on a
rotary evaporator.
3. Adsorb onto 2 g silica gel. Pack the sample on a 2 × 13–cm column (APPENDIX 3E).
4. Elute the column with 50:1 (v/v) CHCl3 /MeOH and check each fraction by TLC
(APPENDIX 3D) using 10:1 (v/v) CHCl3 /MeOH (Rf = 0.24).
5. Collect product fractions and concentrate to a yellow residue on a rotary evaporator.
6. Recrystallize the crude product from 12 mL acetonitrile to yield the white crystal
product.
(±)-cis-[4-(2-Amino-6-cyclopropylaminopurin-9-yl)cyclopent-2-enyl]methanol (aba-
cavir; S.8): 0.19 g (68%). m.p. 74◦ C soften, 154◦ C melt. MS: m/e 287 (m+1)+ . IR
(KBr) (cm−1 ): 3317, 3195, 1594, 1483, 1451. 1 H NMR (DMSO-d6 ): 7.60 (s, 1H, H8),
7.22 (s, 1H, NH), 6.10 and 5.92 (dd, 2H, CH=CH), 5.78 (s, 2H, NH2 ), 5.38 (s, 1H,
H1
), 4.00 (t, 1H, CH2 OH), 3.44 (d, 2H, CH2 OH), 3.00 (m, 1H, NHCH), 2.80 (m, 1H,
H4
), 2.60 (m, 1H, H5
), 1.55 (m, 1H, H5
), 1.55 (m, 4H, CH2 CH2 ). Anal. (C14 H18 N6 O)
C,H,N.

COMMENTARY
Background Information
A major disadvantage of many clinically
used nucleoside drugs is their ability to un-
dergo metabolism or degradation to inactive
forms. For example, most nucleosides are ef-
ficient substrates for nucleoside phosphory-
lases, which cleave the nucleosides at their
N-glycosyl linkage and release the free base
forms. The acid-labile glycosidic linkages are
also easily cleaved by acid in the stomach. To
circumvent these problems, carbocyclic nucle-
osides were designed in which the furanose
ring oxygen of the sugar moiety was replaced
by carbon. As predicted, these non-glycosidic
nucleosides were resistant to both enzymatic
and acid hydrolysis. As a result, many of the
carbocyclic nucleosides exhibit interesting bi-
ological properties and can be used in the areas
of antitumor and antiviral chemotherapy.
Most of the synthetic schemes to car-
bocyclic nucleosides utilize a cyclopentane
or cyclopentene to provide the carbocyclic
sugar. These starting materials are inexpen-
sive and provide the advantage of having an
intact five-membered ring. Several of these
approaches have been described in recent re-
views (Zhu, 2000; Jeong and Lee, 2004). Other
approaches utilizing aristeromycin, ring clos-
ing metathesis, and carbohydrate precursors
are also discussed with their advantages and
disadvantages. For example, the natural prod- Biologically
Active
ucts, aristeromycin and carbohydrates, yield Nucleosides

14.4.7
Current Protocols in Nucleic Acid Chemistry Supplement 25
 chiral products, while the synthetic schemes
are usually long. The use of cyclopentene
precursors have the advantage of short syn-
thetic schemes, but require a resolution step
or the use of a chiral catalyst to obtain the
pure enantiomers. The main advantage of us-
ing the Vince lactam is the relative positioning
of the double bond and the two substituents on
the cyclopentene ring. Opening of the lactam
followed by reduction conveniently provides
the amine group for purine or pyrimidine con-
struction cis to the hydroxymethyl group. It
also places the double bond at the 2,3 position,
which is essential for anti-HIV activity. Other
advantages include the commercial availabil-
ity of both enantiomers from Sigma-Aldrich
and the ease of conversion to the desired nu-
cleosides.
Compound Characterization
NMR spectra were recorded on a 300-MHz
GE spectrometer. Chemical shifts (δ) are given
in part per million (ppm) and referenced to
tetramethylsilane as an internal standard. Cou-
pling constants (J) are given in Hertz and refer
to apparent multiplicities. Elemental analy-
ses were performed by M-H-W Laboratories,
Phoenix, AZ. Melting points were determined
on a Mel-Temp 2 apparatus and are uncor-
rected. Electron impact mass spectra (EIMS)
were obtained with a Kratos/AEI MS-30, and
chemical impact (CI) MS were obtained with
a Finnigan 4000. Thin-layer chromatography
(TLC) was performed on EM Science silica
gel 60 F254 (0.25-mm layer), and column chro-
matography was performed on EM Science
silica gel 60 (230 to 400 mesh).
Critical Parameters and
Troubleshooting
Characterization of the products requires
knowledge of 1 H NMR, UV, and MS. Prior
experience with organic chemistry laboratory
techniques such as recrystallization, solvent
evaporation, extraction methods, TLC, HPLC,
and vacuum filtration is required. All interme-
diates should be stored at 4◦ C and protected
from moisture. Strict adherence to all out-
Synthesis of
Carbovir and
Abacavir from a
Carbocyclic
Precursor
14.4.8
Supplement 25
lined procedures is highly recommended for
safety reasons and for optimum yields of pure
products.
Anticipated Results
These procedures are suitable for prepara-
tion of milligram to multi-gram amounts. The
final products are very stable and can be stored
for several years at room temperature under
anhydrous conditions.
Time Considerations
The synthesis of the final carbocyclic
6-substitued-2-aminopurine nucleosides from
the Vince lactam starting material can be ac-
complished in 2 to 3 weeks.
Literature Cited
Jeong, L.S. and Lee, J.A. 2004. Recent advances
in the synthesis of the carbocyclic nucleosides
as potential antiviral agents. Antiviral Chem.
Chemother. 15:235-250.
Rouhi, A.M. 2003. Cover Story. Chem. Eng. News
81:37-52.
Stinson, S.C. 1994. Market, environmental pres-
sures spur change in fine chemicals industry.
Chem. Eng. News 72:12-26.
Vince, R. and Daluge, S. 1978. Synthesis of
carbocyclic aminonucleosides. J. Org. Chem.
43:2312-2320.
Vince, R. and Hua, M. 1990. Synthesis and anti-
HIV activity of carbocyclic 2
,3
-didehydro-
2
,3
-dideoxy-2,6-disubstituted purine nucleo-
sides. J. Med. Chem. 33:17-21.
Vince, R., Hua, M., Brownell, J., Daluge, S., Lee,
F.C., Shannon, W.M., Lavelle, G.C., Qualls,
J., Weislow, O.S., Kiser, R., Canonico, C.G.,
Schultz, R.H., Narayanan, V.L., Mayo, L.G.,
Shoemaker, R.H., and Boyd, M.R. 1988. Potent
and selective activity of a carbocyclic nucleoside
analog (Carbovir: NSC 614846) against human
immunodeficiency virus in vitro. Biochem. Bio-
phys. Res. Commun. 156:1046-1053.
Zhu, Z.-F. 2000. The latest progress in the syn-
thesis of carbocyclic nucleosides. Nucleosides
Nucleotides Nucleic Acids 19:651-690.
Contributed by Robert Vince and Mei Hua
Center for Drug Design
University of Minnesota
Minneapolis, Minnesota
Current Protocols in Nucleic Acid Chemistry