Nucleic acid related compounds. II. Adenosine 2',3'-ribo-epoxide. Synthesis, intramolecular degradation, and transformation into 3'-substituted xylofuranosyl nucleosides and the lyxo-epoxide

Abstract

Treatment of 2,,3'-0-methoxyethylideneadenosine (1) with excess pivalic acid chloride in refluxing pyridine gave a mixture composed primarily of 6-lV-pivalamido-9-(3-chloro-3-deoxy-2-0-acetyI-5-0-pivalyl-d-D-xylofuranosyljpurine (2a) and 6-lV-pivalamido-9-(3-chloro-3-deoxy-5-0-pivalyl-2-0-[4,4-dimethyl-3-pivalyloxypent-2enoy 1]-ß-d-xylofuranosyl)purine (2b) in high combined yield. Methanolic sodium methoxide converted this mixture to 9-(2,3-anhydro-/3-D-ribofuranosyl)adenine (adenosine ribo-epoxide) (3) in greater than 60% overall yield from starting adenosine. The epoxide 3 was found to spontaneously decompose (presumably via the N3-*^'xylo-cyclonucleoside, i) to the ring-opened aminoimidazole carboxamidine cyclonucleoside ii in water. Sodium hydroxide smoothly effected transformation of ii to the corresponding carboxamide, iii. Pivalylation and benzoylation of 3 in pyridine with the appropriate acid chloride gave 6-M-pivalamido-9-(5-0-pivalyl-2,3-anhydroß-o -ribofuranosyl)purine ( 4) and the corresponding N,N, 08,-tribenzoate, 6, respectively. Tetraethylammonium fluoride in refluxing acetonitrile followed by methoxide deblocking converted 4 or 6 into 9-(3-fluoro-3-deoxy-/3-D-xylofuranosyl)adenine ( 7). Reaction of 6 with sodium benzoate in moist DMF followed by deblocking gave 9-/3-d -xylofuranosyladenine (adenine xyloside) (8) in high yield. Treatment of 6 with sodium azide in hot DMF gave 9-(3-azido-3-deoxy-/3-n-xylofuranosyl)adenine (9a) in excellent yield after removal of protecting groups. Hydrogenation of 9a gave 9-(3-amino-3-deoxy-/3 -d -xylofuranosyl) adenine (9b). Treatment of the crude product [presumably a mixture of N-benzoylated 9-(3,5-di-0-benzoyl-/3-D-xylofuranosyl)adenines] from sodium benzoate

Exploratory Studies to Investigate a Linked Prebiotic Origin of RNA and Coded Peptides

“…As previously mentioned, it was deemed necessary to investigate selective phosphate activation in order to differentiate between 25 and 26 as candidate aminoacyl-RNA trimers (production of 25 and 26 requires activation of CHEMISTRY & BIODIVERSITY ± Vol. 1 (2004) 235 4 ) An additional attractive feature of these anhydro linkages in the xylose series is that they are also known in the purine series (N(3)ÀC(3')), thereby extending nucleobase assembly options [61]. 5 ) The high yields and efficiency of the overall conversion of 81 to 86 are noteworthy and indicate that (pyrimidine) arabinonucleic acid (ANA) should be considered in a prebiotic context.…”

Nucleotides, Part LIX, Synthesis, Characterization, and Biological Activities of New Potential Antiviral Agents: (2′ - 5′)Adenylate Trimer Analogs Containing 3′-Deoxy-3′-(hexadecanoylamino)adenosine at the 2′-Terminus

“…Till 1989 when Samano and Robins [2] reported an efficient nine-step synthesis of 15 in a 66% overall yield, this biologically active compound was isolated either from microbiological cultures or was prepared in very low yields (`2 ± 20%) by chemical means, as, e.g. by transformation [15] [16] of adenosine into 3'-azido-3'-deoxyadenosine (12 steps, overall yields`5%) and further reduction to the 3'-amino component [17], or by coupling reactions of suitable protected purine bases with glucose or xylose derivatives [18] [19] (overall yield2 0%). More efforts by Robins et al [20] led in 1992 to another seven-step synthesis of 15 starting from adenosine via a stereoselective inversion (oxidation/reduction) at C(3'), triflation, azide displacement, and reduction to amine resulting, however, in a much lower overall yield.…”

“…It is recommended to treat dry 1 first with freshly prepared a-acetoxyisobutyryl bromide (2) [21] [22] in moist MeCN [2] [23] [24] leading to a mixture of 9-(2-O-acetyl-3-bromo-3-deoxy-b-d-xylofuranosyl)-and 9-(3-O-acetyl-2-bromo-2-deoxy-b-d-arabinofuranosyl)adenines 3a ± d in which the 5'-OH group is present either in the orthoester function derived from 2,5,5-trimethyl-1,3-dioxol-4(5H)-one (3a, 3c) or in unprotected form (3b, 3d) [15] [16]. The dioxolone and acetyl protecting groups can either be sequentially removed by mild acidic treatment to give from 3a the hydrolysed compound 3b and finally 4 [15] [16] [25], or the mixture of the trans-3'(2')-bromo-2'(3')-acetoxy derivatives 3a ± d was directly treated without further separation with Dowex 1 Â 2 (OH À ) resin in MeOH to give 2',3'-anhydroadenosine (4) in high yield [23 ± 26].…”

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

“…As seen in Fig. 1, the kinetic degradation of 4 (uv A,,,, -270 nm) to product(s) (uv A , , , > 300 nm) in aqueous solution qualitatively parallels that of the analogous adenosine ribo-epoxide (15). However, the reaction proceeds much more readily and attempts to isolate and purify the product were unsuccessful.…”

“…By analogy with the adenosine ribo-epoxide (15), it is assumed that nucleophilic attack by N-1 at C-3' of the epoxide gives transitory N1-+3'-cyclonucleoside formation. Attack of water at C-2 of the positively charged pyrimidine ring followed by ring opening would be expected to lead to an amino carboxamidine substituted pyrrole.…”