An easy access of 2′,3′-dideoxy-3′-α-C-formyl-adenosine and -guanosine analogs via stereoselective CC bond forming radical reaction (original) (raw)
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Helvetica Chimica Acta, 2000
A new type of oligonucleosides has been devised to investigate the potential of oligonucleosides with a nucleobase-including backbone to form homo-and/or heteroduplexes (cf. Fig. 2). It is characterised by ethynyllinkages between C(5') and C(6) of uridine, and between C(5') and C(8) of adenosine. Force-field calculations and Maruzen model studies suggest that such oligonucleosides form autonomous pairing systems and hybridize with RNA. We describe the syntheses of uridine-derived monomers, suitable for the construction of oligomers, and of a dimer. Treatment of uridine-5'-carbaldehyde (2) with triethylsilyl acetylide gave the diastereoisomeric propargylic alcohols 6 and 7 (1 : 2, 80%; Scheme 1). Their configuration at C(5') was determined on the basis of NOE experiments and X-ray crystal-structure analysis. Iodination at C(6) of the (R)-configured alcohol 7 by treatment with lithium diisopropylamide (LDA) and N-iodosuccinimide (NIS) gave the iodide 17 (62%), which was silylated at OÀC(5') to yield 18 (89%; Scheme 2). C-Desilylation of 7 with NaOH in MeOH/H 2 O led to the alkyne 10 (98%); O-silylation of 10 at OÀC(5') gave 16 (84%). Cross-coupling of 18 and 16 yielded 63% of the dimer 19, which was C-desilylated to 20 in 63% yield. Cross-coupling of 10 and the 6-iodouridine 13 (70%), followed by treatment of the resulting dimer 14 with HF and HCl in MeCN/H 2 O, gave the deprotected dimer 15 (73%).
Tetrahedron, 2000
We developed several improved approaches toward 2 H -O-methyl adenosine and guanosine and their N-acyl derivatives. (a) Transglycosylation of N 4 -acetyl-5 H , 3 H -di-O-acetyl-2 H -O-methyl cytidine with N 6 -Bz-adenine provided N 6 -benzoyl-5 H 3 H -di-O-acetyl-2 H -Omethyl adenosine in 50% yield. (b) Regioselective methylation of 2-amino-6-chloro purine riboside with MeI/NaH followed by hydrolysis provided 2 H -O-Me-guanosine in high yield. The same 2 H -O-Me-precursor was transformed into 2 H -O-Me-adenosine in 58% yield. (c) Very efficient transformation of 2,6-diamino-purine riboside into N 2 -isobutyryl (isopropylphenoxyacetyl) 2 H -O-Me-guanosine through methylation of 5 H ,3 H -O-TIPDSi derivative followed by selective N 2 -acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg 2ϩ and Ag ϩ directed methylation of N 1 -Bzl-guanosine proceeded in Ͼ80% yield with ratio of 2 H -O-Me/3 H -O-Me9:1. The same methylation of adenosine with Ag ϩ and Sr 2ϩ acetylacetonates provided 2 H -O-Me-adenosine in 75-80% yield. ᭧
Helvetica Chimica Acta, 2000
A new type of oligonucleosides has been devised to investigate the potential of oligonucleosides with a nucleobase-including backbone to form homo-and/or heteroduplexes (cf. Fig. 2). It is characterised by ethynyllinkages between C(5') and C(6) of uridine, and between C(5') and C(8) of adenosine. Force-field calculations and Maruzen model studies suggest that such oligonucleosides form autonomous pairing systems and hybridize with RNA. We describe the syntheses of uridine-derived monomers, suitable for the construction of oligomers, and of a dimer. Treatment of uridine-5'-carbaldehyde (2) with triethylsilyl acetylide gave the diastereoisomeric propargylic alcohols 6 and 7 (1 : 2, 80%; Scheme 1). Their configuration at C(5') was determined on the basis of NOE experiments and X-ray crystal-structure analysis. Iodination at C(6) of the (R)-configured alcohol 7 by treatment with lithium diisopropylamide (LDA) and N-iodosuccinimide (NIS) gave the iodide 17 (62%), which was silylated at OÀC(5') to yield 18 (89%; Scheme 2). C-Desilylation of 7 with NaOH in MeOH/H 2 O led to the alkyne 10 (98%); O-silylation of 10 at OÀC(5') gave 16 (84%). Cross-coupling of 18 and 16 yielded 63% of the dimer 19, which was C-desilylated to 20 in 63% yield. Cross-coupling of 10 and the 6-iodouridine 13 (70%), followed by treatment of the resulting dimer 14 with HF and HCl in MeCN/H 2 O, gave the deprotected dimer 15 (73%).
Helvetica Chimica Acta, 2000
A new type of oligonucleosides has been devised to investigate the potential of oligonucleosides with a nucleobase-including backbone to form homo-and/or heteroduplexes (cf. Fig. 2). It is characterised by ethynyllinkages between C(5') and C(6) of uridine, and between C(5') and C(8) of adenosine. Force-field calculations and Maruzen model studies suggest that such oligonucleosides form autonomous pairing systems and hybridize with RNA. We describe the syntheses of uridine-derived monomers, suitable for the construction of oligomers, and of a dimer. Treatment of uridine-5'-carbaldehyde (2) with triethylsilyl acetylide gave the diastereoisomeric propargylic alcohols 6 and 7 (1 : 2, 80%; Scheme 1). Their configuration at C(5') was determined on the basis of NOE experiments and X-ray crystal-structure analysis. Iodination at C(6) of the (R)-configured alcohol 7 by treatment with lithium diisopropylamide (LDA) and N-iodosuccinimide (NIS) gave the iodide 17 (62%), which was silylated at OÀC(5') to yield 18 (89%; Scheme 2). C-Desilylation of 7 with NaOH in MeOH/H 2 O led to the alkyne 10 (98%); O-silylation of 10 at OÀC(5') gave 16 (84%). Cross-coupling of 18 and 16 yielded 63% of the dimer 19, which was C-desilylated to 20 in 63% yield. Cross-coupling of 10 and the 6-iodouridine 13 (70%), followed by treatment of the resulting dimer 14 with HF and HCl in MeCN/H 2 O, gave the deprotected dimer 15 (73%).
Stereoselective Syntheses of 3′-Hydroxyamino- and 3′-Methoxyamino-2′,3′-Dideoxynucleosides
Organic Letters
Aminonucleosides are used as key motifs in medicinal and bioconjugate chemistry; however, existing strategies toward 3′-hypernucleophilic amine systems do not readily deliver deoxyribo-configured products. We report diastereoselective syntheses of deoxyribo-and deoxyxylo-configured 3′-hydroxyamino-and 3′-methoxyamino-nucelosides from 3′-imine intermediates. The presence or absence of the 5′-hydroxyl-group protection dictates facial selectivity via inter-or intramolecular delivery of hydride from BH 3 (borane). Protecting group screening gave one access to previously unknown 3′-methoxyamino-deoxyguanosine derivatives.