Sterically Biased 3,3-Sigmatropic Rearrangement of Azides:  Efficient Preparation of Nonracemic α-Amino Acids and Heterocycles

Gagnon, David; Lauzon, Sophie; Godbout, Cédrickx; Spino, Claude

doi:10.1021/ol052034n

Cited by 61 publications

(43 citation statements)

References 39 publications

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“…Methyl Z11,E13-hexadecadienoate was prepared by a Wittig reaction (39). Methyl E10,E12-hexadecadienoate was prepared by coupling methyl 11-undecynoate and (E)-iodo pentene (40). Methyl E10,E12-16,16,16-trideuteriohexadecadienoate was prepared by coupling methyl 11-undecynoate with (E)-2-((4-iodobut-3-enyl)oxy)tetrahydro-2H-pyran (41).…”

mentioning

confidence: 99%

Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

Buček

Matoušková

Vogel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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For sexual communication, moths primarily use blends of fatty acid derivatives containing one or more double bonds in various positions and configurations, called sex pheromones (SPs). To study the molecular basis of novel SP component (SPC) acquisition, we used the tobacco hornworm (Manduca sexta), which uses a blend of mono-, di-, and uncommon triunsaturated fatty acid (3UFA) derivatives as SP. We identified pheromone-biosynthetic fatty acid desaturases (FADs) MsexD3, MsexD5, and MsexD6 abundantly expressed in the M. sexta female pheromone gland. Their functional characterization and in vivo application of FAD substrates indicated that MsexD3 and MsexD5 biosynthesize 3UFAs via E/Z14 desaturation from diunsaturated fatty acids produced by previously characterized Z11-desaturase/conjugase MsexD2. Site-directed mutagenesis of sequentially highly similar MsexD3 and MsexD2 demonstrated that swapping of a single amino acid in the fatty acyl substrate binding tunnel introduces E/Z14-desaturase specificity to mutated MsexD2. Reconstruction of FAD gene phylogeny indicates that MsexD3 was recruited for biosynthesis of 3UFA SPCs in M. sexta lineage via gene duplication and neofunctionalization, whereas MsexD5 representing an alternative 3UFA-producing FAD has been acquired via activation of a presumably inactive ancestral MsexD5. Our results demonstrate that a change as small as a single amino acid substitution in a FAD enzyme might result in the acquisition of new SP compounds.fatty acid desaturase | Manduca sexta | sex pheromone biosynthesis | pheromone evolution | substrate specificity S ex pheromones (SPs) are a diverse group of chemical compounds that are central to mate-finding behavior in insects (1). Variation in SP composition between closely related species and among populations is well documented. Despite this variation, SPs are presumed to be under strong stabilizing selection, and thus the genetic mechanisms driving SP diversification represented an enigma (2). Research on SPs in moths (Insecta: Lepidoptera) helped establish the hypothesis of asymmetric tracking as a major driving force in SP diversification. In this scenario, abrupt changes in female SP composition via a shift in component ratio or the inclusion or loss of a component result in a distinct SP that attracts males with more broadly or differentially tuned SP preference (3). Assortative mating, the preferential mating of females producing a novel SP with males attracted to this SP, restricts gene flow between subpopulations with differing SP compositions. This can ultimately lead to speciation and fixation of novel communication channels (4). Work in insect models such as wasps (5), fruit flies (6), and especially moths (7-9) is helping uncover the genetic basis of SP diversification.In the majority of moth species, females use species-specific mixtures of SP components (SPCs) consisting of volatile fatty acid (FA) derivatives to attract conspecific males at long range. These SPCs are predominantly long-chain aliphatic (C12-C18) acetates, alcoh...

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confidence: 99%

Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

Buček

Matoušková

Vogel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…[11] Eine stereospezifische Reduktion von 8 mit Natriumborhydrid ermöglichte die Synthese des Allylalkohol-Intermediats 9 über lediglich vier Stufen in einer Gesamtausbeute von 23 %. [9] Wir beobachten ausschließlich einen S N 2-und keinen anti-S N 2'-Angriff des Azids auf den Allylalkohol.…”

Section: Angewandte Chemieunclassified

“…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.…”

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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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“…[1] Closely related allylic azides are valuable precursors for allylic amines, as well as for amino acids [2] Correspondence to: F. Dean Toste, fdtoste@berkeley.edu. …”

Section: Introductionmentioning

confidence: 99%

“…We explored the effect of various 3,3′-aryl substituents on the BINAM scaffold, and found that installation of 3,5-dimethyl (A2) or 3,5-bis(trifluoromethyl) (A5) aryl groups at these positions gave improved ee's (entries 2 and 5). Further studies were performed with A5•(AuCl) 2 as the optimal precatalyst, and a crystal structure of the compound was obtained (See Supporting Information).…”

mentioning

confidence: 99%

Enantioselective, Stereodivergent Hydroazidation and Hydroamination of Allenes Catalyzed by Acyclic Diaminocarbene (ADC) Gold(I) Complexes

et al. 2016

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The gold-catalyzed enantioselective hydroazidation and hydroamination reactions of allenes are presented herein. ADC gold(I) catalysts derived from BINAM were critical for achieving high levels of enantioselectivity in both transformations. The sense of enantioinduction is reversed for the two different nucleophiles, allowing access to both enantiomers of the corresponding allylic amines using the same catalyst enantiomer. Graphical AbstractChiral allylic azides and amines may be obtained by enantioselective hydroazidation and hydroamination of allenes catalyzed by acyclic diaminocarbene gold(I) catalysts derived from BINAM. The sense of enantioinduction is reversed for the two different nucleophiles, allowing easy access to both enantiomers with a single catalyst enantiomer. Keywordshydroazidation; hydroamination; enantioselective; gold catalysis; acyclic diaminocarbene Allylic amines are an important functional motif in synthetic organic chemistry and they have been utilized in the synthesis of numerous biologically active compounds. [1] Closely related allylic azides are valuable precursors for allylic amines, as well as for amino acids [2] Correspondence to: F. Dean Toste, fdtoste@berkeley.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript and amine-containing natural products. [3] Allylic azides have typically been prepared via substitution reactions from the corresponding allylic halides, (homo)allylic alcohols, and their derivatives. [4] More recently, Pd-catalyzed C-H activation, [5] and Au-catalyzed hydroazidation of allenes [6] have been employed.While reports of the synthesis of allylic azides are numerous, methods for asymmetric azidation are few. [7] Fewer still are enantioselective hydroazidation reactions, which have only been reported in a formal sense via conjugate addition to activated double bonds (Scheme 1). [8][9][10] In light of recent examples of transition-metal catalysed asymmetric additions of nitrogen nucleophiles to allenes [11] and the growing utility of organic azides, we sought to develop a gold(I)-catalyzed enantioselective hydroazidation of allenes. Cognizant of potential regioselectivity issues from the Winstein rearrangement [12] of the product allylic azides, we initiated our studies using aryl allene 3a. [13] Initial studies revealed that the use of ethereal solvents was critical to obtaining reproducible data. [14] With the choice of solvent established, the enantioinduction afforded by a number of chiral gold(I) catalysts was evaluated under conditions similar to those previously reported, with trifluoroacetic acid (TFA) and trimethylsilyl azide (TMSN 3 ) used for in situ generation of hydrazoic acid (Table 2). [6] Traditional chiral phosphine gold(I) catalysts failed to afford high levels of enantioinduction (entries 1,2) as did a previously reported [15] phosphoramidite catalyst (entry 3). Chiral NHC gold(I) catalysts [16] (entries 4-6) also were found to be unsatisfactory. However, the use of a BINAM-derived ADC gold...

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Sterically Biased 3,3-Sigmatropic Rearrangement of Azides: Efficient Preparation of Nonracemic α-Amino Acids and Heterocycles

Cited by 61 publications

References 39 publications

Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

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

Enantioselective, Stereodivergent Hydroazidation and Hydroamination of Allenes Catalyzed by Acyclic Diaminocarbene (ADC) Gold(I) Complexes

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