2451
J. Org. Chem. 1990,55, 2451-2457
Highly Stereoselective Total Syntheses of 2,5-Anhydro-3-deoxy-and -4-deoxy-~-hexonic Acids and of the Related Deoxyadenosines-C’ Fabrizio Gasparini2 and Pierre Vogel* Institut d e chimie organique d e l’uiniuersitg, CH-1005 Lausanne, Switzerland Received October 5, 1989
(1R,2S,4R)-2-Cyano-7-oxabicyclo[2.2.1] hept-5-en-2-yl (1s’)-camphanate ( 5 ) has been converted into 2,5anhydro-3-deoxy-~-ribo-hexonic acid (8, eight steps, 38% ) and 2,5-anhydro-3-deoxy-~-xylo-hexonic acid (9, seven ((-)-6, derived from (lS,2R,4S)-2-cyan0-7steps, 40%). Similarly, (1S,4S)-7-oxabicyclo[2.2.l]hept-5-en-3-one oxabicyclo[2.2.l]hept-5-en-2-yl(lRq-camphanate (7)) was converted into 2,5-anhydro-4-deoxy-~-ribo-hexonic acid (10, nine steps, 29%) and 2,5-anhydro-4-deoxy-~-xylo-hexonic acid (11, eight steps, 31%). The methods exploit the high regioselectivity of the electrophilic additions of the C=C double bonds in 7-oxabicyclo[ 2.2.11 hept-5-en-2-yl derivatives 5 and 7 (“naked sugars”) and the high exo-face preference for the hydride reduction of 5- and 6-chloro-7-oxabicyclo[2.2.lIhept-5-en-2-ones (21,35). 2’-Deoxyadenosine-C (12) and cordycepin-C (14) were derived from 8 and 10, respectively. Similarly, the corresponding 2’- and 3’-epimers 13 and 15 (C-nucleosides respectively) were obtained in few steps and with deriving from 2-deoxy- and 3-deoxy-P-D-threo-pentofuranose, high stereoselectivity from 9 and 11, respectively.
Under kinetically controlled conditions, the bicyclic homoconjugated ketones 1 add soft electrophiles, EX, to give the corresponding adducts 2 with high regioselectivity.a4 The nucleophile’s (X-) preference for carbon center C(6) was attributed to the electron-releasing effect of the carbonyl function in positively charged intermediates due to the favorable n(C0) aC(2),C(l) pC(6) hyperconjugative interaction.j-’ In contrast, the synthetic precursors 3 of ketones 1 were found to add EX with opposite regioselectivity and to give the corresponding adducts 4 (Scheme I).3,4 This principle has now been applied to the optically pure 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives 5, (+)-6, (-)-6, and 7 (“naked sugars”),8p9which are obtained readily from furan and 1-cyanovinyl camphanates.lOJ1 It has allowed us to develop simple and highly stereoselective total syntheses of all four isomeric 2,5-anhydro-3-deoxyand -4-deoxy-~-hexonicacids 8-11. The latter were converted in two steps and without epimerization at the anomeric center of the pentose moiety into “deoxyadenosines-C” 12-15, C-nucleosides that derive formally from the corresponding 2-deoxy-~-erythro-,2-deoxy-~threo-, 3-deoxy-~-erythro-,and 3-deoxy-~-threo-pentofuranoses.
-
-
Scheme I
7 i)R’
(1) A preliminary communication of this work has been presented at the Journ6es de Chimie Organique (JCO 89),SocieG Franpise de Chimie, Palaiseau, France, Sept 9,1989;communication A 213. Enantiomerically pure 7-oxabicyclo[2.2.l]hept-5-en-2-yl derivatives (“naked sugars”) as synthetic intermediates, Part IX. For Part VIII, see: Bimwala, R. M.; Vogel, P. Helu. Chim. Acta 1989, 72,1825. (2)Present address: Department of Chemistry, Duke University, Durham, NC 27706. (3)Carrupt, P.-A.; Vogel, P. Tetrahedron Lett. 1982,23,2563-2566; Helu. Chim. Acta 1989,72, 1008-1028. (4)Black, K. A.; Vogel, P. J. Org. Chem. 1986,51, 5341-5348. (5) Carrupt, P.-A.; Vogel, P. Tetrahedron Lett. 1984,25,2879-2882. ( 6 ) Carrupt, P.-A.; Vogel, P. J. Phys. Org. Chem. 1988, I , 287-298. (7) Carrupt, P.-A,; Gabioud, R.; Rubello, A,; Vogel, P.; Honegger, E.; Heilbronner, E. Helu. Chim.Acta 1987, 70,1540-1550. (8)Warm. A,; Vogel, P. J. Org. Chem. 1986,51,5348-5353. (9)Vogel, P.; Auberson, Y.; Bimwala, M.; de Guchteneere, E.; Vieira, E.; Wagner, J. In Trends in Synthetic Carbohydrate Chemistry;Horton, D., Hawkins, L. D.,McGarvey, G. J., Eds. ACS Symposium Series 386; American Chemical Society: Washington, DC, 1989; Chapter 13, pp 197-241. (10) Vieira, E.; Vogel, P. Helu. Chim.Acta 1983,66,1865-1871. (11)Warm, A.; Vogel, P. Helu. Chim. Acta 1987,70,69&700. See also: Black, K. A.; Vogel, P. Ibid. 1984,67,1612-1615.Saf, R.; Faber, K.; Penn, G.; Griengl, H. Tetrahedron 1988,44, 389-392.
x2
1
(-1-6
R = (1R)camphanoyl
Starting with 2-deoxy-~-erythro-pentose, Igolen and co-workers12prepared 2’-deoxyadenosine-C (12) in seven steps (3.9% overall yield) via the mixture of CY- and p-furanoside cyanides 17 and the corresponding imidazoles 18 following an approach similar to that they had developed for the synthesis of adenosine-C (16).13 El Khadem and El Ashry14 transformed D-xylose (15 steps, 6.2% overall yield) into cordycepin-C (14) according to a method similar to that reported earlier by Bobek and Farkas’j for the synthesis of adenosine4 and which implies the pyrolysis at 220-225 “C of amide 19 obtained by condensation of (12)Kolb, A.; Gouyette, C.; Huynh-Dinh, T.; Igolen, J. Tetrahedron 1975,31,2914-2920. (13)Huynh-Dinh, T.; Kolb, A,; Gouyette, C.; Igolen, J. J . Heterocycl. Chem. 1975. 12. 111-117. (14)El Khadem, H. S.; El Ashry, E. S. H. Carbohydr. Res. 1973,29, 525-527; 1974,32,339-348. (15)Bobek, M.: Farkas, J. Collect. Czech. Chem. Commun. 1969,34, 241-252.
0022-3263/90/ 1955-2451$02.50/0 C 1990 American Chemical Society
2452
Gasparini and Vogel
J. Org. Chem., Vol. 55, No. 8, 1990
'*&1
OR
8 R=H
CI
9 R=H 27 R=Bn
HovwH 32 R=Bn
RO
11 R=H 40 R=Bn
FN
20
((1Spcamphanic acid)
\
2
/
c
Y
14 X=H,Y=OH 15 X=OH.Y=H
12 X=H,Y=OH 13 X=OH,Y=H
FN
N$NH2
HO OH
16 ("adenosine-C")
10 with 4,5,6-triaminopyrimidine.16 In the case of the synthesis of 16, this latter technique led to epimerization at the "anomeric" center.15 C-Nucleosides 13 and 15 are unknown compounds.
9 1s
17 H2N
Fl6 R=Bn +9
OMe
o
v
N
H
R
19
Results One-pot transformation of the "naked sugar" 5 into chloro enone 21 (Scheme 11) was achieved in 94% yield via adduct 20, oxidative elimination of the benzeneselenyl moiety with H20z,and saponification of the camphanate. At this stage, (1s)-camphanic acid (chiral auxiliary) was recovered with a yield better than 85%.8 Reduction of ketone 21 with NaBH4 in MeOH at -10 "C afforded the endo alcohol 22 (8570)'~ contaminated with less than 3% of the exo isomer. O z ~ n o l y s i of s ~the ~ ~chloroalkene ~~ 22 (16)For a shorter and highly stereoselective synthesis of cordycepin-C, see: Gasparini, F.; Vogel, P. Helu. Chim. Acta 1989, 72, 271-277. (17)Durgnat, J.-M.; Vogel, P. Unpublished.
M
~
e
O
t-
p e
32
C
3;)
H N
OBn 31
\8 28 X=OH. Y=H -13 33 X=H. Y=OH -12
R'=
30
HZN
in MeOH followed by a workup with NaBH,18 led to the expected methyl 2,5-anhydro-~-hexonate(23) in mediocre yield (40-5070). The use of Me2S in the workup of the ozonolysis product led to the formation of acetal-ester 24 in 88% yield. Under the same conditions, the benzyl ether 25 (derived from 22) gave the fully protected methyl 2,5anhydro-4-deoxy-L-rylo-hexuronate 26 in 90% yield. When the ozonolysis was carried out at a temperature above -65 "C, the benzyl ether was partially oxidized into the corresponding benzoate. Acidic hydrolysis (THF/ H20/HzS04,70 "C) followed by treatment with N&H,CN (20 "C) afforded the partially protected 2,5-anhydro-4deoxy-D-xylo-hexonic acid (27) in 88% yield. Hydrogenolysis of the benzyl ether (H2/Pd/C, THF/H20) gave 9 (95%). Condensation with 4,5,6-triaminopyrimidinegave amide 28 (55%), which on heating in DMF (130 "C) in the presence of CsF16afforded the new C-nucleoside 13 in 94% yield. Mitsunobu20 substitution of the endo alcohol 22 (PhCOOH, Ph3P, diethyl azodicarboxylate) failed to give the corresponding exo-benzoate. However, treatment of 22 with (CF,SOz)zO and pyridine21 yielded triflate 29 (85%), which was displaced smoothly by BnOLi in THF/HMPT to give the exo benzylic ether 30 (74%). Ozonolysis of 30 in MeOH (-78 "C) followed by a workup with Me# afforded 31 (86%),which was hydrolyzed and reduced (as for 26 27) into 32 (94%). Hydrogenolysis of 32 furnished 2,5-anhydro-3-deoxy-~-ribo-hexonic acid (8) (96%). Condensation with 4,5,6-triaminopyrimidine gave amide 33, which, on heating with CsF/DMF (130 0C),16,23was dehydrated into the known 2'-deoxyadenosine-C (12)12 (Scheme 11).
Hov-Nu OH
22 R=H 25 R=Bn 29 R=CF,SO,
23
21
Y
Y
L/
24 R=H
H
p
21
+ R'OH
?e
HovN HovN y
&
C
HoBcooHHowcwMe 4 .1 fin -
10 R=H 49 R=Bn
N
OR'
Scheme I1
-
(18)Gender, W.J.; Chan, S.; Ball, D. B. J . Am. Chem. SOC.1975,97, 436-437. Gender, W.J.;Chan, S.; Ruchirawat, S. J . Org. Chem. 1981, W.J.; Chan, S.; Ball, D. B. Ibid. 1981, 46, 3407-3415. (19)For other examples of chloroalkene ozonolysis, see: Keul, H.; Griesbaum, K. Can. J . Chem. 1980, 58, 2049-2054. Schneider, H.; Griesbaum, K. Tetrahedron Lett. 1979, 57-58. Griesbaum, K.; K e d , H. Angew. Chem. 1975,87, 748-749. Schulte-Hostede, S.;Gab, S.; Korte, F. Chem. Ber. 1978,111, 2646-2655. Gab, S.;Nitz, S.; Parlar, H.; Korte, F. Angew. Chem. 1976,88, 479-480. (20) Mitsunobu, 0. Synthesis 1981, 1-28. (21)Binkley, R. W.; Ambrose, M. G.; Hehemann, D. G. J . Org. Chem. 1980, 45, 4387-4391. (22)de Guchteneere, E.;Vogel, P. In preparation. (23)Boiling 4,5,6-triamino-N-acylpyrimidines in 1.5 N NaOH is known to induce the formation of the corresponding purine^.^' Under these conditions, our amides gave low yields of the expected C-nucleosides together with products of decomposition. (24)Smith, C. V. Z.; Robins, R. K.; Tolman, R. L. J . Chem. Sot., Perkin Trans. 1 1973, 1855-1858. 46, 1750-1752. Gender,
Stereoselective Total Syntheses of D-Hexonic Acids
J. Org. Chem., Vol. 55, No. 8, 1990 2453
Scheme 111
24
35
J.
IS I4
--
I
IIX=OKY=H 19X=H,Y=OH
3:)
H2N R'=
HP
OB"
U
The addition of PhSeCl to enone (-)-6 gave exclusively adduct 34. Treatment with m-chloroperoxybenzoic acid (mCPBA) afforded chloro enone 35: which was reduced (NaBH,/MeOH, -10 "C) into endo alcohol 36 (less than 2% of the corresponding exo isomer was formed by 360-MHz 'H NMR of the crude reaction mixture). When the same procedures were followed as those presented for the syntheses of 12 and 13 (Scheme II), the new C-nucleoside 15 and cordycepin-C (14)" were obtained in good yields (Scheme III; see Experimental Section). Electrochemically induced oxidative decarbo~ylation~~ in MeOH of the deoxy-whexonic acids 8-11 furnished the corresponding methyl deoxy-D-pentofuranosides45 (go%), 46 (93%), 47 (E'/%), and 48 (95%). Hydrolysis (0.25 M H2S04/H20,EO "C) afforded 2-deoxy-D-erythro-pentose (73% )?6 2-deoxy-D-threo-pentose 3-deoxy-Derythro-pentose (61%)?* and 3-deoxy-D-threo-pentose
Figure 1. CD spectra of C-nucleosides 12 (A, in H,O), 13 (B,in H,O), 14 (C, in MeOH) and 15 (D,in MeOH).
(86%),29respectively, whose characteristics were identical with those reported in the literature for these carbohydrates." The structures of all the new compounds presented here were established hy their elemental analysis, spectral data, mode of formation, and reactivity. The CD spectra of the new C-nucleosides 13 and 15 had the same signs and were similar (see Figure 1) to those measured for 1212and 14, thus confirming the p relative configuration of the "anomeric centers". It is interesting to note that while the mass spectra of amides 19,28,33, and 41 displayed base peaks at m / e = 125 amu corresponding to the 4,5,6-tri-
with Dsrabinose. see: Id K&t. PI W.; h w e y , M.; Wiggins. L F. J Chem. Soc 1919.I232-1235. (b) Allemn. R.: Overend, W . C . lbid. 1951, 148&1484 la Peller~son.L.: Freid. T.:Maenurson. (;. J. Ore. Chem. 1984.49. 4 5 4 k 5 4 1 (six s&, 46?0$. Start& with'D-xvlme:' (d) Anderson. C. D.: Goodman. L.rBaker. B. R. J . .& ('hem .-.Sot. 1959.81, 896-902. (e) Wnlton, E.; Holly. F. W.; Rorer. G . E.;Nut. R. R.: Jenkins. S R. J . Mid. Chem. 1965. 659 463 (seven stem. 22901. in Nair. V.: ~~.R..~ Sinhababu, A. K. J . Org. Chem. 1978; 43, 5013-jbli (eight steps, 42%): (9) Witnak, 2. J.; Whistler, R. L. Carbohydr. Res. 1982,110,326329 (six aupa. 2 2 . 7 % ~See also: (hl De Hernard". S.; 'l'engi. J. P.; Sasao, G . J.; W+ IKPIP.M. J. O ~ KChem . 1985.50,3457-3462. Starting with o-glucose: ( I , SmbG. P.;SmbS. I . J Chum. Sur 1965,2944-291s teieht SWDS. 8%). Staning with 2 . 3 - 0 - i s o p r o p y l i d ~ n ~ . ~ g l y ~ ~(ir ~ & d r~ehi &yrd. ~ S. L.; C u u I ~ t ,M 'r. Tetrahedron La[. 19x7. 2b. IU4S-1046. Starting with furan. (kr I t o , Y.;Shihara, T.: Aiira. M.: Siawai. H.. Ohno, M. J. Am. l'hrm. Sor. 1981. IOJ, TiSH741. (I1Ohno. M.: Ito. Y.; hila.M..Shihara T.;Adachi, K.; Sawai, H. Tetrahedron 19&1,40,145-152 (five steps,
