branched-chain sugar nucleosides. iii. 9-(3-deoxy-3- c -methyl-β- ...

Branched-chain sugar nuc1eosides.l 111. 9-(3-Deoxy-3-C-methyl- P-D-allofuranosyl and ribofuranosy1)adenine

ALEX ROSENTHAL AND MATEJ SPRINZL Department of Cl~emistry, U~ziuersity of British Colunzbin, Vancouver, B.C.

Received May 20, 1969

Condensation of triphenylphosphinemethylene (Wittig reagent) with 5-0-benzyl-1,2-0-isopropylidene-a-D-erythro-pentafuranos-3-uloe and with 1,2:5,6-di-O-isopropylidene-a-~-ribo-hexofuranos-3- ulose (1) afforded 5-O-benzyl-l,2-O-isopropylidene-3-deoxy-3-C-methylene-a-~-ribofuranose in 36% yield and 1,2:5,6-di-O-isopropylidene-3-C-methylene-a-~-ribo-hexofuranose (2) in 55% yield, respec- tively. A detailed study of the affect of reaction conditions on the yield of the unsaturated sugar is described. Hydrogenation of 2 proceeded stereoselectively to yield 4 which was hydrolyzed selectively to the 1,2-0-monoisopropylidene derivative 5. Benzoylation of the latter gave 6 which was converted by acetolysis to the 1,2-diacetate 7. Condensation of this compound with 6-benzamidochIoromercuri- purine in the presence of titanium tetrachloride followed by deblocking with methanolic sodium methoxide, yielded 9-(3-deoxy-3-C-methyl-8-D-allofuranosy1)adenine (10) in 48 % yield based o n 7. Sodium metaperiodate oxidation of 10, followed by sodium borohydride reduction of the aldel~ydo derivative, afforded 9-(3-deoxy-3-C-methyl-p-D-ribofuranosy1)adenine (11) in 85 % yield.

Canadian Journal of Chemistry, 47, 3941 (1969)

Interest in 3'-deoxyribofuranosyl nucleosides stems partly from the fact that 3'-deoxyadenosine (cordycepin, the first isolated nucleoside antibi- otic) inhibits nucleic acid synthesis in Ehrlich ascites cells (1,2). The recent synthesis of 3'-C- methyladenosine (3) and the finding that it also exhibits biological activity, has further stimulated a concern in the nucleoside antibotics. Branched- chain sugar nucleosides have recently been pre- pared from 3-deoxy-3-C-hydroxymethyl-D-ery- throfuranose (4). Our laboratory has been inter- ested in developing a gensral method of synthesis of branched-chain sugar nucleosides (5), and in particular, the synthesis of 3'-deoxy and 2'-deoxy branched-chain sugar nucleosides having the ribofuranosyl skeleton in the sugar moiety. In this paper we wish to report the synthesis of several deoxy branched-chain sugar nucleosides and in particular, the synthesis of a structural analogue of cordycepin by application of a Wittig reaction to ketoses.

The readily available 1,2:5,6-di-0-isopropylidene-a-D-ribo-hexafuranos-3-ulose (1) (6,7) is a useful intermediate for the synthesis of 3-deoxy- 3-C-substituted branched-chain sugars. In a previous communication (8) we described the application of the modified Wittig reaction to 1 to afford a 3-hydroxyethyl substituted branched- chain sugar, and in this paper we report the application of the basic Wittig reaction to the ketose 1. Condensation of triphenylphosphinemethy-

'For papers I and 11 see references 20 and 21.

lene with 1 in the ratio 3 :1 using methyl sulfoxide as solvent (9,lO) gave 1,2:5,6-di-0-isopropylidene-3-C-methylene-a-D-ribo-hexofuranose (2) in 55% yield, and in addition, a by-product 3 of unknown constitution. Compounds 2 and 3 were separated by column chromatography on silica gel. The yield of 2, as shown in Table I, was de- pendent on the reaction conditions. In all cases the reaction was monitored by thin layer chromatography (t.1.c.) and stopped when all ketose (except in procedure 5) was consumed. When the temperature was increased from 22" to 60°, the yield of by-product was significantly increased and the yield of 2 decreased to 23 %. On the other hand, use of an equimolar ratio of ketose and ylid (see procedure 4) led to a significant decrease in the yields of both products. When 1,2-di- methoxyethane (glyme) was used as a solvent, elevated temperature (60") was required and the maximum yield of unsaturated sugar was 28 %. From the results shown in procedures 2 and 3 it would appear that the yield of 2 is approximately the same when the ketose is added to the ylid as when all the reactants are mixed together at the beginning of the reaction.

Product 3 reacted slowly with bromine in car- bon tetrachloride to give an unstable halide. It also reacted with potassium permanganate but absorbed less than 0.2 mole equivalent of hydrogen over palladium. Attempts to purify it by preparative t.1.c. on silica gel led to degradation as evidenced by the fact that 3 was converted into a mixture of three new substances. Compound 3 did not contain any phosphorus or sulfur. Based

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

162.

220.

120.

214

on 1

1/10

/14

For

pers

onal

use

onl

y.

CANADIAN JOURNAL OF CHEMISTRY. VOL. 47, 1969

TABLE I Wittig reaction of triphenylphosphinemethylene with 1,2:5,6-di-0-isopropylidene-a-D-ribo-

hexofuranose (1) to yield unsaturated sugar 2 and by-product 3 --

Ketose:Ylid Temperature Yield 2 Products 2 Procedure ratio Solvent ("c) Time (h) % and 3 ratio

1 :3 DMSO 60 2 23 2:l 1 :3 DMSO 22 5 53 3:1 1 :3 DMSO 22 1 55 3:1 1 :1 DMSO 22 5 30 1O:l

*Ketose added directly to the mixture of methyltriphenylphosphonium bromide, sodium hydride, and methyl sulfoxide. tMethyltriphenylphosphonium bromide converted into the ylid before addition of the ketose.

on the work of Walling and co-worker (1 1) and the molecular weight of 3 (determined from its mass spectrum), it might be inferred that side products from methyl sulfoxide might have added to the ketose to afford addition products. The great difficulty in isolating sufficient material of sufficient stability to do structural work led us to abandon this phase of the research.

Hydrogenation of 2 using palladium on charcoal proceeded stereoselectively to afford, after high vacuum distillation, compound 4 in 75% yield. The configuration of C-3 of 4 was readily ascertained from its nuclear magnetic resonance (n.m.r.) spectrum. The H-2 signal of 4 appears as a triplet (resolved into two doublets under mag- nification) showing that H-2 is coupled to H-3 and to H-I. On the other hand, in the gluco- furanose series (12) there is no coupling between H-2 and H-3, thus leading to a doublet for H-2. Therefore, the only possible configuration for C-3 is the allo-configuration. This was further proved by spin-spin decoupling experiments. Ir- radiation of H-2 of 4 collapsed H-1 into a singlet and altered H-3. Therefore, 4 is undoubtedly 1,2:5,6- di - 0- isopropylidene - 3 - deoxy - 3 - C - methyl-a-D-allofuranose.

Selective hydrolysis of the 5,6-0-isopropylidene group of 4 to yield 5 in 81 % yield was ac- complished using aqueous methanol containing sulfuric acid. Benzoylation of the latter gave the dibenzoate 6 in 94% yield which was purified by column chromatography on silica gel. Acetolysis of 6 with acetic acid, acetic anhydride, and sulfuric acid for 3 days gave mainly the p-anomer 7 in 82% yield. Condensation of the latter with 6- benzamidochloromercuripurine by the titanium tetrachloride method (13) afforded the blocked allo-nucleoside 9. Deacylation of 9 using methan-

olic sodium methoxide afforded crystalline P- nucleoside 10 in 48% yield based on 7. The assignment of structure and anomeric configuration to 9-(3-deoxy-3-C-methyl-P-D-allofuranosy1)-adenine (10) was based on the following: ( I ) ultraviolet (u.v.) absorption data of 10 substantiates the site of glycosylation (14) at N-9, (2) the trans rule (15) indicates that 10 has a P-configuration, and (3) the allo-nucleoside 10 exhibits a negative Cotton effect that is consistent with the proposals advanced (16,17) for assignment of structure to purine nucleosides. The mother liquor from 10 was carefully investigated by paper chromatography and also by column chromatography on Dowex 1 x 2 (OH-) (18) using gradient elution but the presence of any a-anomer of 10 was not detected.

Sodium metaperiodate oxidation of the allo- nucleoside 10 yielded an aldehyde-nucleoside that was immediately reduced with sodium borohydride to yield the crystalline ribo-nucleoside 11 in 85 % yield. Surveillance of the degradation reaction using a starch-iodine test was essential to minimize production of a by-product which was difficult to remove. Based on the fact that the allo-nucleoside 10 was degraded to the ribo- nucleoside 11 by steps which are known not to alter the configuration of sugars, therefore, 11 can be assigned the structure 9-(3-deoxy-3-C- methyl-P-D-ribofuranosy1)adenine. In the latter nucleoside, n.m.r. evidence (H-1' gave a doublet having J , , , , , = 1.5 Hz) corroborates the p-anomeric configuration of 11.

The general applicability of the Wittig reaction for preparingmethyl analogues of cordycepinwas demonstrated by condensing 5-0-benzyl-1,2-0- isopropylidene - a - D - erythro - pentafuranos - 3 - ulose (19) with triphenylphosphinemethylene to

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

162.

220.

120.

214

on 1

1/10

/14

For

pers

onal

use

onl

y.

ROSENTHAL AND SPRINZL: BRANCHED-CHAIN SUGAR NUCLEOSIDES. 111

HO-CH2 BzO-CH2

HO- I

BzO- I

H,O+ BZ c l ___f

e Me Me Me

4 5 Me 6

AcOH 1 H30+

I BzO-

OAc

yield, after column chromatography on silica gel, 5 - 0 - benzyl - 1,2 - 0 - isopropylidene - 3 - deoxy - 3-C-methylene-a-D-ribofuranose in 36 % yield.

Experimental General Considerations

Nuclear magnetic resonance (n.m.r.) spectra were obtained on deuteriochloroforn1 solution (unless otherwise stated) with tetramethylsilane as the internal standard (set at T 10) using a Jeolco 60, a Varian A-60, or Varian

HA-100 spectrometers. Mass spectroscopy was obtained with an A.E.I. M.S.9 spectrometer. The ultraviolet (u.v.) spectral measurements were performed on a Cary 140 spectrophotometer. The optical rotary dispersion (0.r.d.) measurements were performed on a Jasco Model ORD/ UV-5 Spectropolarimeter at room temperature on aqueous solutions. All melting points (micro hot stage) are corrected. Silica gel G was used in the thin layer chronlatography (t.1.c.). For column chromatography Silica gel Woelm 100-200 mesh, activity grade 11, was used. Elemental analyses were performed by the Micro- analytical Laboratory, University of British Columbia.

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

162.

220.

120.

214

on 1

1/10

/14

For

pers

onal

use

onl

y.

3944 CANADIAN JOURNAL OF ( 3HEMISTRY. VOL. 47, 1969

Applicatiotz of Wittig Reactiotz to 1,2:5,6-Di-0- isopropylidetze-a-D-ribo-lzexofioanos--oe ( I ) to Yield 1,2:5,6-Di-0-isopropylidetze-3-C-tnetlzyletze- a-D-ribo-hexofi~ratzose (2)

Sodium hydride (0.240 g, 0.01 mole) was suspended in 30 ml of anhydrous methyl sulfoxide and the mixture was heated at 75" for 45 rnin in a dry box in an anhydrous nitrogen atmosphere. After the solution was cooled to 20" methyltriphenylphosphonium bromide (3.95 g, 0.011 mole) was added and the mixture stirred for 30 min. T o the resulting mixture was added dropwise with stirring (with external cooling at 20") a solution of 1,2:5,6-di- 0-isopropylidene-a-D-ribo-hexofuranos-3-uoe (0.84 g, 0.0033 mole) in 10 ml of anhydrous methyl sulfoxide. After the addition, the reaction mixture was stirred for an additional 2 h and then poured into 100 ml water. The aqueous solution was extracted with 5 separate portions of 30 ml ether. The combined ether extracts were washed with water (5 x 30 ml), dried over magnesium sulfate, filtered, and evaporated under reduced pressure to yield a syrup. This syrup was dissolved in petroleum ether (50 ml, b.p. 60-90") and then left stand overnight at 0". Triphenylphosphonium oxide was removed by filtration and washed with several small portions of cold petroleum ether. The combined filtrate and washings were evaporated under reduced pressure to yield a syrup (0.760 g). Thin layer chromatography on silica gel G using benzene-ethyl acetate (20:l) as developer and 2 % potassium permanganate o r sulfuric acid as detector revealed two spots having Rf's of 0.6 and 0.5. The syrup was separated by column chromatography (60 x 1.5 cm diam) on silica gel using 100 ml of benzene followed by 600ml of benzene-ethyl acetate (9:l) as developer. Aliquots were collected on a fraction collector and analyzed by t.1.c. as described above. Evaporation of the eluents afforded compound 2 (0.458 g, 55 % yield) and a second faster moving fraction 3 (0.140g, 17% yield).

Compound 2 showed no carbonyl in its infrared (i.r.) spectrum. It showed the presence of a methylene group (1660 cm-I); t (CDCI,), 4.2 (I-H, d, J1,2 = 4.5 Hz due to H-1), 4.55 (1-H, m, due to H-3), 5.1 (1-H, d, J,,, = 4.5 Hz, due to H-2), 6.0 (m, due to H-4, H-5, and H-6), 8.5 (12-H, t, due to isopropylidene groups); the compound was homogeneous by vapor phasechromatography (v.p.c.) at 160"; t.1.c. R, 0.5, + 104" (c, 2, chloroform).

Anal. Calcd. for C13HzOO5: C, 60.90; H, 7.84. Found: C, 61.13; H, 8.00.

The faster moving component 3 (R, 0.6) was recrystal- lized from petroleum ether (b.p. 35-60"), m.p. 35-37", and sublimed at 50 OC (0.056 mm pressure), - 174" (c, 2, chloroform). Mass spectroscopy: 304, 289. The n.m.r. spectrum showed t (CDCI,), 3.7-4.1 (I-H, m), 4.44.9 (I-H, m), 5.7-6.0 (m), 8.5 (12-H, due to isopropylidene groups); i.r., 1660 cm-l. The compound was unstable a t room temperature or on rechromatography on silica gel G (gave three new compounds). Attempts to hydrogenate this substance were unsuccessful (less than 0.2 mole equivalent of hydrogen was absorbed).

1,2:5,6-Di-O-isopropylidene-3-deoxy-3-C-methyl-cr-~- alloficratzose (4)

Compound 2 (1.024 g) dissolved in methanol (30 ml),

was allowed to react with hydrogen at room temperature and 1 atm pressure using 10% palladium on charcoal (0.2 g) as catalyst until the gas pressure remained con- stant (86 nil of hydrogen absorbed). Work-up of the product 4 in the usual way followed by distillation under high vacuum (b.p. 77-80" at 0.05 mm) gave an oil, yield 0.765 g (7573, which was homogeneous by v.p.c. (at 160") and by t.1.c. (benzene-ethyl acetate, 20:1), R, 0.5. The n.m.r. spectrum showed t (CDCl,), 4.25 (H-1, d, J1,, = 3.7Hz), 5.50 (H-2, t, JIS1 = 3.7Hz and J,,, = 3.7 Hz), 5.9-6.4 (m, due to H-4, H-5, and H-6), 8.1 (m, due to H-3), 8.6 (t, due to isopropylidene groups), 8.4 (d, due to H-3', J,,,, = 7 Hz). Irradiation of H-3 collapsed the doublet at 8.5 p.p.m. to a singlet; [aIDZ2 +37" (c, 1, chloroform).

Anal. Calcd. for C13Hzz05: C, 60.40; H, 8.52. Found: C, 60.28; H, 8.52.

5-O-Benzyl-l,2-O-isopropylidetze-3-deoxy-3-C-methyletze- a-D-ribofrrranose

Application of the Wittig reaction to 5-0-benzyl-1,2-0- isopropylidene-a-D-erytliro-pentafuranos--uoe as described in the first part of the experimental gave after column chromatography of the product 5-0-benzyl-1,2- O-isopropylidene-3-deoxy-3-C-methylene-cr-~-ribofuranose in 36% yield, 7 (CDCI,), 4.12 (d, H-1, J,,, = 4 Hz), 4.5-4.8 (m), 5.1 (d, due to =CHI), 5.42 (s, due to 0-CH2C6H5), 6.04 (m, due to H-5), 8.55 (d, due to isopropylidene group), R, = 0.55 (benzene-ethyl acetate 10:1), [ C L ] , ~ ~ +63O (c, 1, chloroform).

Anal. Calcd. for Cl6HZ0OO: C, 69.60; H, 7.26. Found: C, 70.02; H, 7.15.

1,2-O-Isopropylidet1e-3-deoxy-3-C-methyl-ci-~- allofuratzose (5)

To a solution of 0.520 g of 4 in 4 ml of methanol was added 4ml of 0.1 Nsulfuricacid. After thereaction mixture was left standing a t room temperature for 3.5 h it was neutralized with barium hydroxide ( p H kept at 7), boiled, and filtered through Celite. The filtrate was evaporated to dryness and the residue dissolved in 20 ml water. The solution was extracted with 5 ml chloroform to remove a trace of 4. After the water solution was again evaporated to dryness the residue was extracted with 3 x 20 ml of boiling chloroform. The combined chloroform extracts were dried over magnesium sulfate, filtered, and evaporated to dryness, yield 0.356 g (81 %) of a syrup, R, = 0.45 (benzene-methanol 3:1), + 35" (c, 1, chloroform).

5,6-Di-O-benzoyl-l,2-O-isopropylidene-3-deoxy-3-C- methyl-a-D-allofuratlose (6)

T o a solution of 5 (0.870 g) in pyridine (10 ml) was added dropwise freshly distilled benzoyl chloride (1 ml). After the reaction mixture was kept at room temperature overnight it was poured into water, and the product extracted with chloroform in the usual way, yield 1.48 g (94%). Fractionation of the crude product on silica gel (80 x 2 cm diam) with 20:l benzene-ethyl acetate gave 1.35 g of product which was dissolved in methanol to yield a glass, R, = 0.6 (10:l benzene-ethyl acetate), t (CDCI,), 1.9-2.5 (10-H due to phenyl), 4.15 (d, H-I, J1 ,, = 3.5 Hz), 8.0 (m, due to H-3), 8.8 (d, due to H-3', J,,,. = 7 Hz), [(zIDz2 + 32' (c, 1, chloroform).

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

162.

220.

120.

214

on 1

1/10

/14

For

pers

onal

use

onl

y.

ROSENTHAL AND SPRINZL: BRANCI 3D-CHAIN SUGAR NUCLEOSIDES. 111 3945

Anal. Calcd. for CZ4HZ6o6: C, 70.3; H, 6.39. Found: C, 70.5; H, 6.72.

1,2- Di-O-acetyl-5,6-di-O-benzoyl-3-deoxy-3-C-tnetlzyl- a@)-D-allofurar~ose (7)

To a well-stirred solution (kept at 0") of 6 (1.230 g) in glacial acetic acid (15 ml) and acetic anhydride (1.5 ml) was added dropwise 0.82 ml of concentrated sulfuric acid. After storage at room temperature for 4 days the solution was poured into 50 ml of vigorously stirred mixture of ice and water. The resulting mixture was extracted with chloroform (2 x 20 ml), the chloroform extracts washed with 20 ml of water, aqueous sodium bicarbonate, water, dried over magnesium sulfate, filtered, and evaporated to dryness in vacuo to give 1.12 g (83%) of a syrup 7;

00 (c, 2, chloroform), T (CDCI,), 3.95 (s, due to H-1), 4.75 (d, H-2, J,., = 5.2 HZ).

9-(3-Deoxy-3-C-met~1yl-~-~-allofurattosyl)-adetine (10) A mixture of 1.35 g (0.003 mole) of sugar 7, 1.60 g

(0.0037 mole) of 6-benzamidochloromercuripurine (8), and 1 g of Celite and anhydrous xylene (20 ml) was dried by distilling off the xylene under reduced pressure. To the resulting residue was added 50 ml of anhydrous ethylene dichloride and 15 ml of the solvent was distilled. To the partially cooled mixture was added a solution of 0.338 ml of titanium tetrachloride in 4 ml of ethylene dichloride, and the reaction mixture was heated under reflux for 4 h. The cooled reaction mixture was then poured into 50 ml of saturated sodium bicarbonate and stirred vigorously for 30 min, and then filtered through Celite. The Celite cake was washed with chloroform, and the combined organic extracts washed with 15 ml of 30% aqueous potassium iodide and 15 ml of water. After evaporation of the solvent under reduced pressure the residue was dissolved in 30 ml methanol and the resulting solution decolorized with charcoal, filtered through a Celite column, and then evaporated to dryness under vacuo to give 0.98 g (52 %) of the blocked nucleoside 9, Rl = 0.32 using 1 :2 benzenexthyl acetate as developer. Compound 9 was deacylated by refluxing with 15 ml of 0.05 N inethanolic sodium methoxide for 4 h. The cooled solution was neutralized with glacial acetic acid and left stand overnight at 00. The unblocked nucleoside 10 was removed by filtration, yield 0.275 g. The mother liquor was evaporated under reduced pressure and the residue dissolved in 20 ml water. The aqueous solution was then extracted with 2 x 10 ml ether. Passage of the aqueous solution through a Dowex 1 x 2 (OH-) column (15 x 1 cm diam) followed by elution with water (to remove inorganic ions), 30% methanol, and finally 60% methanol (total about 200 ml) afforded 0.090 g of 10 in the last fraction. No observable amount of the a-anomer of 10 was found in any fraction of the eluent. Recrystallization of combined 10 from 80% methanol-water afforded 0.35g (79 %) of crystalline 10, m.p. 227-228", - 25" (c, 1, water), h.,,,(H20) (mp) 261 (E 18,250), RI (adenine) 0.96 on Whatman paper No. 1 using water as developer. The 0.r.d. spectrum of 10 showed a negative Cotton effect, [$I270 -7800, [$126~ Vr [4124, +975' (c, 1.0 x

in water), h (D20, a t 60"); 4.08 (d, H-1', J,,, = 2.5 Hz), 7.45 (m, H-37, 8.85 (d, CH,, J,,,, = 6 HZ).

Anal. Calcd. for C12H170SN4: C, 48.80; H, 5.80; N, 23.72. Found: C, 48.65; H, 5.77; N, 23.88.

Sodium Metaperiodate Oxidation and Reduction of the Allo-tlucleoside 10 to Yield 9-(3-Deoxy-3-C- tnetlzyl-13-D-ribofuranosy1)-adet~ine (11)

To a solution of the all0 nucleoside 10 (0.295 g, 0.001 mole) in 30 ml of water and 15 ml of ethanol was added with stirring a 5 % aqueous solution of sodium metaperiodate (0.214 g, 0.001 mole). The progress of the reaction was monitored by the starch-iodine test (com- pared with a blank). It was essential to avoid use of excess oxidant as this caused a significant decrease in yield of 11. The solution was kept at neutral p H with saturated sodium bicarbonate solution (about 0.5 ml). The reaction mixture was left standing at room temperature in the dark for 2 h. T o the resulting solution was added with stirring sodium borohydride (0.300 g) and the mixture stirred for 3 h. Excess of sodium borohydride was decomposed by addition of glacial acetic acid. The reaction mixture was evaporated under reduced pressure and the residue treated with 3 x 5 ml of methanol followed by evaporation. The crystalline residue was dissolved in 2% acetic acid (5 ml) and applied onto a column of Dowex 50 (NH4+) resin (15 ml of 1 cm diam column). The inorganic ions were eluted with 300 ml water and the nucleoside was then eluted with 5 % ammonium hydroxide. Evaporation of the solvent followed by recrystallization of 11 from 80% methanol-water gave 0.225g of 11 (85%), m.p. 231-232", [a],'' -36" (c, 1, water), h,,,(H,O) 261 (E 13,400), R,,,,,,, 1.2; T (deuterio- methylsulfoxide) 1.68 (s, H-2), 1.95 (s, H-8), 2.82 (s, NHz), 4.15 (d, H-1', J,,,,. = 1.5 Hz), 4.4 (d), 5.0 (m), 5.75 (m), 6.4 (nl), 8.4 (m near DMSO peak), 9.1 (d, CH,, J3,,, = 7 Hz).

Anal. Calcd. for Cl lHls03N5: C, 49.80; H, 5.70; N, 26.40. Found: C, 49.87; H, 5.74; N, 26.57.

Acknowledgment

This work was supported by the N a t i o n a l Re- sea rch Counc i l of Canada.

1. H. KLENOW and S. FREDERIKSEN. Biochim. Biophys. Acta, 87, 495 (1964).

2. (a) S. S. COHEN. Prom. NucI. Acid Res. Mol. Biol. 5,.1 (1967) and references cited therein; (b) J. J. Fox, K. A. WATANABE, and A. BLOCH. Progr. Nucl. Acid Res. Mol. Biol. 5, 251 (1967).

3. E. WALTON, S. R. JENKINS, R. F. NUTT, M. ZIMMER- MAN, and F. W. HOLLY. J. Amer. Chem. Soc. 88, 4524 (1966).

4. E. J. REIST, D. F. CALKINS, and L. GOODMAN. J. Amer. Chem. Soc. 90. 3852 (1968).

5. A. ROSENTHAL. ~ d v a n . ~ a r b o h y d . Chem. 23, 59 (1968).

6. P. J. BEYNON, P. M. COLLINS, and W. G. OVEREND. Proc. Chem. Soc. 342 (1964).

7. (a) K. ONODERA, S. HIRANO, and N. KASHIMURA. J. Amer. Chem. Soc. 87,4651 (1965); (b) K. ONODERA, S. HIRANO, and N. KASHIMURA. Carbohyd. Res. 6 , 276 (1968).

8. A. ROSENTHAL and L. NGUYEN. Tetrahedron Let- ters. 2393 (1967).

9. E. J. CORA and M. CHAYKOVSKY. J. Amer. Chem. SOC. 84, 866 (1962).

10. R. GREENWALS, M. CHAYKOVSKY, and E. J. COREY. J. Org. Chem. 28, 1128 (1963).

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

162.

220.

120.

214

on 1

1/10

/14

For

pers

onal

use

onl

y.

3946 CANADIAN JOURNAL OF CHEMISTRY. VOL. 47, 1969

11. C. WALLING and L. BOLLYKY. 1. Org. Chem. 28, 16. T. R. EMERSON, R. J. SWAN, and T. L. V. ULBRICHT. 256 (1963); J. Org. Chem. 29, 2699 (1969). Biochem. Biophys. Res. Commun. 22, 505 (1966).

12. R. J. ABRAHAM, L. D. HALL, L. HOUGH, and K. A. 17. T. MISHIMURA, B. SHIMIZU, and I. IWAI. Biochem. MCLAUCHLAN. J. Chem. Soc. 3699 (1962). Biophys. Acta, 157, 221 (1968).

13.5. PROKOP and D. H. MURRAY. J. Pharm. Sci. 54, IS. A. P. MARTINEZ, W. W. LEE, and L. GOODMAN. J. 359 (1965). Org. Chem. 34, 92 (1969).

14. J. M. GULLAND and E. R. HOLIDAY. J. Chem. Soc. 19. A. ROSENTHAL and D. A. BAKER. Tetrahedron Let- 765 (1936). ters, 397 (1969).

15. (a) R. S. TIPSON. J. Biol. Chem. 55, 130 (1939); 20. A. ROSENTHAL and L. (BENZING) NGUYEN. J. Org. (b) B. R. BAKER. Chemistry and biology of purines. Chem. 34, 1029 (1969). Ciba Foundation Symposium. Little, Brown and Co., 21. A. ROSENTHAL, M. SPRINZL, and H. J. KOCH. Can. Boston, Mass. 1957. p. 157. J. Chem. 47, 3263 (1969).

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

162.

220.

120.

214

on 1

1/10

/14

For

pers

onal

use

onl

y.

branched-chain sugar nucleosides. iii. 9-(3-deoxy-3- c -methyl-β- ...

Documents