Oligoribonucleotide Synthesis. II. Preparation of 2′-O-tetrahydropyranyl Derivatives of Adenosine and Cytidine Necessary for Insertion in Stepwise Synthesis

Abstract

The syntheses of N6-benzoyl-2'-0-tetrahydropyranyladenosine (2) and N4-benzoyl-2'-O-tetrahydropyranylcytidine (11) and their corresponding 5'-0-p-methoxytrityl derivatives, 3 and 12 respectively, are described. Compounds 2, 3, 11, and 12 are the protected derivatives of adenosine and cytidine required for insertion into a new oligoribonucleotide synthesis. Compound 2 was prepared from the known 2'-0-tetrahydropyranyladenosine by perbenzoylation followed by de-0-benzoylation. Compound 11 is prepared from cytidine by the following sequence: orthoacetate protection of the 2'-and 3'-hydroxyls; benzoylation of the 5'-and NJ-positions; orthoacetate ring opening provided a mixture of the 2'-and 3'-monoacetates from which the major, 3'-0-acetyl-N4,5'-0-dibenzoylcytidine (7) was isolated; dihydropyran treatment on the 2'-hydroxyl of 7 and subsequent selective deacylation studies were carried out. Specific de-0-acylation gave 11.

Oligoribonucleotide synthesis. X. An improved synthesis of the anticodon loop region of methionine transfer ribonucleic acid from E. coli

“…~~-~enzo~l-2'-0-meth~lcy'tidine (2) was prepared from 3'-0-acetyl-N4-5'-0-dibenzoylcytidine (17) (12). Diazomethane treatment of 17 gave the corresponding 2'-0-methyl ether (18) in 87% yield.…”

“…sluggish and highly coloured, probably the result Suitably protected nucleosides, 1 (lo), 4 (1 1) of pyridine hydrochloride generation. In an 6 , 11 (12), and 9 (13), had been prepared preeffort to overcome these practical difficulties, the viously. Each heterocyclic base (except uracil) coupling agent, mesitylenesulfonyl 1,2,4-tri-carried a benzamido grouping and each riboazolide (MST) (9) was used in all later phos-furanoside 2'-hydroxyl was protected by a phorylation and coupling reactions.…”

Selective deacylation of peracylated ribonucleosides

“…Several reagents have been developed toward this end including (a) sodium methoxide used in the original Khorana approach, 13 (b) aqueous sodium hydroxide in pyridine, 14,15 and (c) dilute methanolic ammonia. 16 Most of these methods furnish the target nucleosides in moderate to good yield.While exploring an alternative route toward N2 0 -functionalized 2 0 -amino-a-L-LNA (Locked Nucleic Acid) monomers, 17 we needed facile access to thymine derivative 1 17b (Scheme 1). Chemoselective N3-benzoylation of O2 0 -unprotected nucleoside 2 18 using direct N-acylation, 19 phase transfer conditions, 20 or transient protection protocols 11 only resulted in low yields of 1 (<50%) due to formation of O2 0 -benzoylated and/or O2 0 ,N3-dibenzoylated products.…”

“…Several reagents have been developed toward this end including (a) sodium methoxide used in the original Khorana approach, 13 (b) aqueous sodium hydroxide in pyridine, 14,15 and (c) dilute methanolic ammonia. 16 Most of these methods furnish the target nucleosides in moderate to good yield.…”

Oligoribonucleotide Synthesis. VI. Selective Deblocking of the 5′-O-Triphenylmethoxyacetyl Grouping in Protected Dinucleotides

“…A summary in the general case is outlined: Phosphorylation of 2 using the pyridinium salt of P,P,P-trichloroethylphosphate (6) and TPS, and subsequent coupling with the higher RF diastereoisomer of 1 (1,7,8) gives the protected dinucleotide XpY2 (3) in yields >50"/, except when G is involved (ca. 30%).…”