Reactions of 2-acyloxyisobutyryl halides with nucleosides. II. Reactions of adenosine

Abstract

2 ',3 . (a). Perchloric acid (0.1 ml, 70%) was added to a stirred suspension of uridine (2.44 g, 10 mmol) in acetonitrile (10 ml) and acetaldehyde (5 ml) at room temperature. After 45 min a clear solution resulted and the solvents were removed in vacuo leaving 4 g of an oily solid. The latter was extracted several times with hot chloroform in order to remove aldehyde polymers leaving 1.9 g (70%) of crystalline 35. Recrystallization from ethanol gave 1.50 g (56%) of 35 with mp 194-196°u nchanged upon recrystallization (reported80 mp 194-195 °); XrH 260 nm (e 9900).(b). A solution of uridine (244 mg, 1 mmol) and 4 (0.49 g, 3 mmol) in DMF (1 ml) was kept at room temperature for 10 min. Solid sodium borohydride (300 mg) was added portionwise (frothing), and the semisolid mass was then diluted with chloroform, washed three times with aqueous bicarbonate and then water, dried, and evaporated leaving 370 mg of a syrup. This was treated for 1 hr with methanol-concentrated ammonium hydroxide (1:1, 4 ml) and then evaporated to dryness. The residue was separated into four bands by preparative tic using chloroform-methanol (9:1). The slower bands corresponded to uridine and 2'-chloro-2'-deoxyuridine while elution of the next band gave 43 mg (16%) of 35 which spontaneously crystallized. Recrystallization from methylene chloride gave 30 mg of a diastereomeric mixture of 35 with mp 183-185°. The nmr spectrum of the major isomer corresponded to that above while the minor isomer was readily distinguished by the appearance of CvH as a doublet (Jv%> = 2 Hz) at 6.32 ppm and of C¿H as a doublet (J5,e = 8 Hz) at 7.86 ppm.

Nucleic acid related compounds. 24. Transformation of tubercidin 2′,3′-O-orthoacetate into halo, deoxy, epoxide, and unsaturated sugar nucleosides

“…La N-pivalamido-4 (pivaloxymethyl-5 furanyl-2)-7 pyrrolo[2,3-dlpyrimidine (IOU) est produire lors du chauffage de 3c ou §a. DCblocage de 10a donne 1Bd qui est hydrogCnC et donne le racCmique amino-4 (didCoxy-2,3 B-D,L-glyccropentofuranosy1)-7 pyrrolo[2,3-dlpyrimidine (7,11). Le nuclCoside insaturC-2',3' (6) est obtenu et, hydrogCnC, donne la didCoxy-2',3' tubercidine (7).…”

“…The use of free radical dechlorination conditions (10) (tri-12-butyltin hydride plus a,al-azobisisobutyronitrile as initiator) with 3a followed by deblocking gave 3'-deoxytubercidin (8) (5,6) in 517, yield. This allows use of the blocked chloro nucleosides for syntheses of specific deoxy derivatives whereas catalytic hydrogenolysis of chloro compounds has been generally unsuccessful (6,11). Treatment of the unpurified mixture of 3a,3b with methanolic sodium methoxide gave the ribo-epoxide (2',3'-anhydrotubercidin) (4) (6,8) in 72% overall yield from 1.…”

Nucleic acid related compounds. 25. Syntheses of arabino, xylo, and lyxo-anhydro sugar nucleosides from tubercidin ribo-epoxide

“…Bt was found to be more experimentally convenient and economical to use the iodo product 2, obtained by treatment of tubercidin (I) with a-acetoxyisobutyryi chloride and excess sodium iodide (5b). This is in contrast with reactions involving ader~osine in which the orthoester] pivalyl chloride route proceeds sn-~oothly (5d) and avoids problems of incomplete reaction, multiple acylation, and significant glycosyl bond cleavage noted with the Mattocks-Moffatt procedure (6,7). 6 2 situ generation of cx-acetoxyisobutyryl iodide in acetonitrile provided smooth reaction with I at room temperature to give 4-amino-7- (2) in quantitative yieid (56) (see Scheme 1).…”

“…This is in contrast with reactions involving ader~osine in which the orthoester] pivalyl chloride route proceeds sn-~oothly (5d) and avoids problems of incomplete reaction, multiple acylation, and significant glycosyl bond cleavage noted with the Mattocks-Moffatt procedure (6,7). 6 2 situ generation of cx-acetoxyisobutyryl iodide in acetonitrile provided smooth reaction with I at room temperature to give 4-amino-7- (2) in quantitative yieid (56) (see Scheme 1). Treatment of the amorphous product (2) with methanolic ammollia at room temperature gave the ribo-epoxide (3) …”

Nucleosides. 118. Total syntheses of pentopyranine B and D. Cytosine nucleosides elaborated by Streptomyces griseochromogenes

“…Acetylation of the iodohydrin afforded the crystalline acetate 2. Hydrogenation of 2 over Pd/C gave a product which was contaminated with considerable amounts of 2,3-and 3,4-dideoxysugars (13). However, reduction of 1 gave the corresponding 3-deoxysugar (3) which was acetylated to give the crystalline methyl 2-0-…”