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PMC:7291971 / 12306-17424 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T75 0-14 Sentence denotes 2.2 Chemistry
T76 15-255 Sentence denotes The retrosynthetic analysis of the dinucleoside 1 structure suggested the coupling reaction between the tosyl derivative 17 previously described by us (Scheme 2) [14], and the readily accessible 5′-amino-2′,3′-isopropylidene adenosine [21].
T77 256-471 Sentence denotes The direct N-alkylation at room temperature did not afford the secondary amine in satisfactory yields and when increasing the temperature to enhance the reactivity of the primary amine, we noticed degradation of 17.
T78 472-668 Sentence denotes To circumvent the lack of reactivity of primary amines, a synthetic method using nitrobenzenesulfonamides (Ns-amides) as both a protecting and activating group has been developed by Fukuyama [22].
T79 669-782 Sentence denotes The main advantage of this nosyl strategy is that both alkylation and deprotection proceed under mild conditions.
T80 783-968 Sentence denotes Recently, the 2-nitrobenzenesulfonamide has been used successfully to synthetize transition state analogs of DNA methylation based on the coupling of cytosine analogs to adenosine [15].
T81 969-1093 Sentence denotes In the same way, we envisaged the coupling between 17 and the 5′-nosyl adenosine 18 to obtain the dinucleoside 1 (Scheme 2).
T82 1094-1363 Sentence denotes The building block 18 was prepared in 74% yield by reacting 4-nitrobenzenesulfonyl chloride [22] that has a similar reactivity to 2-nitrobenzenesulfonyl chloride as used in Ref. [15], with 5′-amino-2′,3′-isopropylidene adenosine prepared upon published procedures [23].
T83 1364-1522 Sentence denotes N-alkylation of Ns-amide 18 with 17 in the presence of K2CO3 in DMF at room temperature did not afford the expected dinucleoside 19, even at high temperature.
T84 1523-1675 Sentence denotes Nevertheless, according to the literature [24], the addition of a catalytic amount of KI to the reaction mixture was beneficial to give 19 in 74% yield.
T85 1676-1798 Sentence denotes Facile deprotection of 19 by treatment with a nucleophilic thiolate produced the desired secondary amine 20 in high yield.
T86 1799-1909 Sentence denotes Removal of sugar protecting groups has been accomplished in acidic medium to give dinucleoside 1 in 76% yield.
T87 1910-2075 Sentence denotes Likewise, the acidic treatment was applied to the intermediate Ns-amide 19 to afford the 4-nitrobenzenesulfonamide-containing dinucleoside 9 in 34% yield (Scheme 2).
T88 2076-2266 Sentence denotes Compounds 2, 3 and 4 were obtained from key compound 20 via reductive amination of the aldehyde 21 that was prepared in three steps from l-aspartic acid following a published procedure [25].
T89 2267-2370 Sentence denotes Reductive amination was conducted in the presence of sodium triacetoxyborohydride and acetic acid [26].
T90 2371-2450 Sentence denotes The resulting fully protected dinucleoside 22 was isolated in high yield (93%).
T91 2451-2556 Sentence denotes Then, sugar hydroxyls and amine were deprotected by TFA treatment and afforded methyl ester derivative 3.
T92 2557-2719 Sentence denotes Subsequent basic treatment with LiOH converted the methyl ester in carboxylic acid and dinucleoside 2 with α-amino acid chain similar to that of SAM was obtained.
T93 2720-2903 Sentence denotes Finally, the SAM analogue 4 with an amide function instead of a carboxylic acid in α-amino acid chain was prepared from 22 upon a final treatment with 7 M methanolic ammonia solution.
T94 2904-3161 Sentence denotes Dinucleosides 5, 6 and 7 were rather synthesized through N-alkylation of 20 with 1-bromobutane, 1-bromo-3-phenylpropane or methyl-4-bromobutyrate, respectively, in N-methylmorpholine in the presence of diisopropylethylamine (DIEA) at 110 °C under microwave.
T95 3162-3273 Sentence denotes These specific conditions were optimized for a successful synthesis of 23, 24 and 25 with an average 50% yield.
T96 3274-3385 Sentence denotes This moderate yield results from double N-alkylations (observed in mass spectrometry) and incomplete reactions.
T97 3386-3471 Sentence denotes Increasing temperature of the reactions neither did drive the reaction to completion.
T98 3472-3583 Sentence denotes Next, 23, 24 and 25 were deprotected upon TFA treatment to obtain N-alkyl derivatives 5, 6 and 7, respectively.
T99 3584-3751 Sentence denotes Subsequently, an additional basic treatment with 2 M LiOH was applied to 7 to convert the methyl ester moiety into the carboxylic acid-ended alkyl chain of compound 8.
T100 3752-3952 Sentence denotes The same synthetic route used for the preparation of nosyl-containing dinucleoside 9 was followed to synthesize compounds 10–13 with diverse Ns-amide moieties as analogs of the nosyl group (Scheme 3).
T101 3953-4222 Sentence denotes The reaction of 5′-amino-2′,3′-isopropylidene adenosine [23] with four diversely substituted (OMe, CF3, Cl) and commercially available nitrobenzenesulfonyl chloride reagents afforded the corresponding N-nosyl adenosines 26–29 with 40–72% yield [[27], [28], [29], [30]].
T102 4223-4366 Sentence denotes Their subsequent coupling with 17 in the presence of K2CO3 and KI gave the corresponding dinucleosides 30–33 in moderate yields from 43 to 52%.
T103 4367-4517 Sentence denotes A final TFA treatment provided the respective N-nosyl adenine dinucleosides 10–13 which were purified by reversed-phase chromatography (Yield 13–20%).
T104 4518-4643 Sentence denotes Scheme 4 depicts the synthesis of the adenine dinucleosides 14–16 from the intermediate NH-linked dinucleoside 20 (Scheme 2).
T105 4644-4772 Sentence denotes The reaction of 4-chlorobenzenesulfonyl chloride with 20 in the presence of NEt3 [31,32] followed by a TFA treatment yielded 14.
T106 4773-5001 Sentence denotes The treatment of 20 with 4-chloro-3-nitrobenzaldehyde or 4-chlorobenzaldehyde and sodium triacetoxyborohydride, followed by the removal of protective groups in acidic conditions resulted in dinucleosides 15 and 16, respectively.
T107 5002-5118 Sentence denotes It is noteworthy that this reductive amination conducted at 40 °C increased the yields to 71% and 81%, respectively.