A stereoselective and efficient route to (3S, 4R, 5S)-(+)-4,5-dihydroxycyclopent-1-en-3-ylamine: the side chain of the hypermodified nucleoside Q

Ovaa, Huib; Codée, Jeroen D. C.; Lastdrager, Bas; Overkleeft, Herman S.; Marel, Gijsbert A. van der; Boom, Jacques H. van

doi:10.1016/s0040-4039(98)01738-9

Cited by 39 publications

(22 citation statements)

References 15 publications

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“…Next, the acetonide protecting group was cleaved (70 % acetic acid, 40 °C, 20 h) to give the diol. The hydroxy groups were protected as bulky tert ‐butyldimethylsilyl (TBS) ethers (TBSCl, pyridine, 40 °C) to control the stereochemistry of the epoxidation reaction and to avoid potential future Payne rearrangements 13,14. The epoxide was subsequently prepared from cyclopentene 9 by using meta ‐chloroperoxybenzoic acid ( m ‐CPBA; CH 2 Cl 2 , 0 °C → r.t.).…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of the Hypermodified tRNA Nucleoside Epoxyqueuosine

Thoma

Carell

2013

Eur J Org Chem

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Queuosine is one of the most strongly modified nucleosides found in transferRNA (tRNA) of almost all species. Queuosine is found exclusively in the wooble position of the anticodon loop of several tRNA, where it is involved in tRNAAsp, tRNAAsn tRNAHis, and tRNATyr. The biosynthesis of queuosine is performed by prokaryotes, and eukaryotes are fully dependent on this external source. To investigate the interesting biosynthesis of the Q base, we report here the first total synthesis of the direct biosynthetic precursor oQ. By using LC–MS in combination with special E. coli growing conditions (no vitamin B12 in the medium) we confirm the structure of the oQ natural products.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of the Hypermodified tRNA Nucleoside Epoxyqueuosine

Thoma

Carell

2013

Eur J Org Chem

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“…The unusual selectivity of the Mitsunobu amination is further demonstrated by the observation that the use of the diastereomeric allylic alcohol 11 14 provides the same allyl azide 4 and, after Staudinger reduction, the allylic amine 2 . This result is only explainable if, in this case, we assume an interesting, and for the Mitsonobu amination untypical, syn ‐S N 2′ reactivity 15.…”

Section: Methodsmentioning

confidence: 95%

Synthesis of the Transfer‐RNA Nucleoside Queuosine by Using a Chiral Allyl Azide Intermediate

Klepper¹,

Jahn²,

Hickmann³

et al. 2007

Angew Chem Int Ed

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Transfer RNAs (tRNAs) are key molecules needed for the decoding of the genetic information at the ribosome.[1] The tRNAs contain the four canonical RNA bases plus a large set of modified nucleotides whose function in the tRNA charging and decoding process is largely unknown.[2] Queuosine (Q; 1) [3] and its galactosylated, mannosylated, or amino acid modified derivatives [4] (Scheme 1) are important hypermodified RNA bases present in the anticodon stem loop of various tRNAs. It is currently hypothesized that these base derivatives are needed to fine-regulate the translational process.[5]To enable investigation of the role that these hypermodified bases play during the translational process and to study their largely unknown biosynthesis, [6] efficient synthetic procedures for the modified bases and ultimately of tRNA containing such modified bases are a prerequisite.Herein we describe an efficient stereoselective synthesis of the hypermodified tRNA nucleoside queuosine [7] using a reductive amination of 7-deazaguanosine-aldehyde 3 with the cyclopentenylamine 2, [8] which is prepared from an allyl azide precursor (Scheme 1).The short synthesis of the allyl amine 2 from the allyl azide precursor 4, however, requires that the Mitsunobu reaction (Scheme 2, step e) [9] proceeds with a defined regio-(S N 2 vs. S N 2') and stereochemistry (inversion of configuration). In addition, the [3.3] sigmatropic rearrangement, which allyl azides such as 4 are prone to undergo, has to be controlled.[10] Indeed, owing to the efficient [3.3] sigmatropic rearrangement of allylic azides and the reported lack of regiocontrol of Mitsunobu aminations of allylic alcohols, [19] such a synthetic approach looks, at first, rather unattractive.The cyclopentenyl building block 2 was synthesized starting from d-(À)-ribose 5. Protection of the 2' and 3' hydroxy groups as an acetonide, conversion into the monoScheme 1. Chemical structures of queuosine (1), its derivatives, and key synthetic intermediates. Bz = benzoyl.Scheme 2. Synthesis of the cyclopentenylamine 2: a) 2,2-dimethoxypropane, MeOH, HClO 4 , acetone, 94 %; b) PCC (4.0 equiv), benzene, reflux, 46 %; c) (MeO) 2 P(O)CH 3 , nBuLi, THF, 0 8C, 56 %; d) NaBH 4 , CeCl 3 , MeOH, 0 8C, 95 %; e) DIAD, PPh 3 , HN 3 (1.3 m in toluene), THF, 0 8C; f) PPh 3 , THF, 0 8C, 72 % (65 % from 11) in two steps; g) toluoyl chloride, NEt 3 , CH 2 Cl 2 , 60 %. PCC = pyridinium chlorochromate, DIA-D = diisopropylazodicarboxylate.

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“…Die ungewöhnliche Selektivität der Mitsunobu-Aminierung zeigt sich auch darin, dass bei Verwendung des diastereomeren Allylalkohols 11 [14] ebenfalls das Allylazid 4 und nach der Staudinger-Reduktion das Allylamin 2 entstehen. Dies ist nur erklärbar, wenn wir in diesem Fall eine für Mitsunobu-Aminierungen untypische syn-S N 2'-Reaktivität annehmen.…”

Section: Angewandte Chemieunclassified

Synthese des tRNA‐Nucleosids Queuosin unter Verwendung eines chiralen Allylazid‐Intermediats

et al. 2007

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Transfer-RNAs (tRNAs) sind Schlüsselmoleküle für den Prozess der Dekodierung genetischer Information im Ribosom.[1] Sie enthalten die vier kanonischen RNA-Basen und eine große Zahl an modifizierten Nucleotiden, deren Funktion im Prozess der tRNA-Beladung und -Dekodierung größtenteils unbekannt ist.[2] Queuosin (Q) 1 [3] und seine galactosylierten, mannosylierten und Aminosäure-modifizierten Derivate [4] (Schema 1) sind wichtige hypermodifizierte RNA-Basen, die in der Antikodonschleife verschiedener tRNAs vorliegen. Es wird derzeit vermutet, dass sie für die Feinregulierung des Translationsprozesses benötigt werden. [5] Will man die Aufgabe der hypermodifizierten Basen bei der Translation besser verstehen und ihre größtenteils unbekannte Biosynthese untersuchen, [6] benötigt man effiziente Syntheserouten zu diesen Basen und letztlich zur tRNA, in der sie enthalten sind.Wir beschreiben hier eine effiziente, stereoselektive Synthese des hypermodifizierten tRNA-Nucleosids Queuosin.[7] Dabei wird als Schlüsselschritt eine reduktive Aminierung des 7-Desazaguanosinaldehyds 3 mit dem Cyclopentenylamin 2, [8] das aus der Allylazid-Zwischenstufe 4 hervorgeht, durchgeführt (Schema 1).Die vorgestellte kurze Synthese des Allylamins 2 ausgehend von der Vorstufe 4 setzt jedoch voraus, dass die Mitsunobu-Reaktion (Schema 2, Stufe e) [9] nach einer definierten Regio-(S N 2 gegenüber S N 2') und Stereochemie (Umkehr der Konfiguration) abläuft. Zusätzlich muss die [3.3]-sigmatrope Umlagerung kontrolliert werden, der Allylazide wie 4 unterliegen.[10] Ein derartiger Ansatz scheint zunächst -bedingt durch die effiziente [3.3]-sigmatrope Umlagerung der Allylazide und die bekannte [19] fehlende Regiokontrolle der

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A stereoselective and efficient route to (3S, 4R, 5S)-(+)-4,5-dihydroxycyclopent-1-en-3-ylamine: the side chain of the hypermodified nucleoside Q

Cited by 39 publications

References 15 publications

Total Synthesis of the Hypermodified tRNA Nucleoside Epoxyqueuosine

Total Synthesis of the Hypermodified tRNA Nucleoside Epoxyqueuosine

Synthesis of the Transfer‐RNA Nucleoside Queuosine by Using a Chiral Allyl Azide Intermediate

Synthese des tRNA‐Nucleosids Queuosin unter Verwendung eines chiralen Allylazid‐Intermediats

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