L‐Erythruronic Acid Derivatives as Building Blocks for Nucleoside Analogs. Synthesis of 4′‐<i>C</i>‐Aryl‐D‐ribonucleosides

A new bifunctional ligand capable of promoting various enantioselective catalytic transformations has been prepared by connecting a bis(oxazoline) to dihydroquinidine via a spacer. This ligand has been employed in a one-pot procedure, in Enantioselective catalytic transformations represent invaluable tools in modern organic synthesis. [1] Many of these processes are dependent on the use of chiral ligands that, in combination with various metals, promote highly stereoselective reactions. Some ligands can be employed in a variety of processes. For instance, metal complexes of chiral bis(oxazoline)s (box) [1] have been used in enantioselective DielsϪAlder, hetero DielsϪAlder, and 1,3-dipolar cycloadditions, in cyclopropanations and aziridinations, in Mukaiyama-aldol and MukaiyamaϪMichael additions, in allylations, hydrocyanations, and hydrosilylations of carbonyl compounds, and in reduction and oxidation reactions. [2] In principle, further extension of the versatility of box ligands might be achieved by attaching such species to a residue capable of exerting stereocontrol over other catalytic transformations. This approach would also provide the appealing opportunity of using the new bifunctional ligand in sequential processes. [3Ϫ8] With this goal in mind, the bis(oxazoline)Ϫ dihydroquinidine (box-DHQD) adducts 1a,b were synthesized (Scheme 1). Esters and ethers of DHQD 2 have been shown to be powerful ligands for the asymmetric dihydroxylation [9] and aminohydroxylation [10] reactions developed by Sharpless. Moreover, compounds structurally related to DHQD have been employed in other enantioselective catalytic processes, [11] including alkylations, epoxidations, Michael additions, and β-lactam syntheses. [12] Reaction of 2 with 6-bromohexanoyl chloride in the presence of triethylamine gave ester 3 in quantitative yield. This was reacted [13] with the metalated box ligands 4a (R ϭ Ph) and 4b (R ϭ tBu) to afford compounds 5a,b in yields of 55% and 53%, respectively. Since disubstitution at the bridging carbon atom of box ligands has proved to be essential to achieve a high degree of stereocontrol in many box-promoted reactions, [2] 5a,b were methylated to give the adducts 1a,b in yields of 33% and 30% (47% and 45% based on recovered 5a,b), respectively. [14] It is important to note [a] 1045 which the asymmetric cyclopropanation and dihydroxylation of styrene were accomplished in a sequential fashion with good enantioselectivity. Scheme 1. Synthesis of box-DHQD ligands 1a,bReagents and conditions: (a) Br(CH 2 ) 5 COCl, Et 3 N, CH 2 Cl 2 , room temp., 15 h; (b) metalation of 4a,b: 1.0 mol equiv. of BuLi, 0.5 mol equiv. of (iPr) 2 NH, 1.0 mol equiv. of TMEDA, THF/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidone (DMPU) 1:3, Ϫ50°C, 30 min; then 4a or 4b (1.0 mol equiv.); Ϫ50°C, 2.0 h; alkylation: 1.0 mol equiv. of 2, Ϫ50°C to room temp., 15 h; (c) metalation: as in (b) on 1.0 mol equiv. of 5a,b; alkylation: 1.6 mol equiv. of MeI, Ϫ50°Cto room temp., 56 h that the bridging carbon atom in box ligands 1a,b is not stereog...

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“…Cyclopropane 7 (11 mg) was obtained in 40% yield, diol 8 (15 mg) in 71% yield. Their 1 H NMR spectra were identical to those re- [20] }.…”

Section: Synthesis Of Box-dhqd (1b)mentioning

confidence: 59%

Synthesis of a Bifunctional Ligand for the Sequential Enantioselective Catalysis of Various Reactions

Annunziata¹,

Benaglia²,

Cinquini³

et al. 2001

Eur. J. Org. Chem.

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“…Starting from ribose, addition of phenyllithium on a 1,4-ribonolactone derivative followed by a N -glycosidation allowed the synthesis of the corresponding 1- C -phenyl nucleoside analogues and the corresponding bicyclo derivatives [13,14,15,16,17]. Another strategy was developed for the preparation of 4'- C -phenyl nucleoside analogues using addition of phenyllithium or phenylmagnesium bromide on a lactol followed by N -glycosidation [19]. Tricyclonucleoside analogues were obtained in a multi-steps strategy starting from D-glucose and D-xylose.…”

Section: Discussionmentioning

confidence: 99%

“…Introduction of all four nucleobases were realized using similar strategy giving compounds 55 – 60 and two of them were selectively deprotected to obtain the β-isomers 61 and 62 (Figure 3). In 1982, Vasella and co-workers reported the synthesis of 4'- C -aryl-D-ribonucleosides as synthons for the synthesis of antibiotics [19]. Starting from the 1,4-lactone derivative 64 obtained from the ribonolactone 63 in two steps, addition of an excess of 2-methoxymethoxyphenyllithium at 10 °C afforded two isomeric lactones 65 and 66 in 65% yield with an excess of the L-lyxo 66 (54%).…”

Section: Addition Of An Aromatic Ring To a Carbonyl Groupmentioning

confidence: 99%

“…Vasella and co-workers have also reported in the same paper described above the use of phenylmagnesium bromide instead 2-methoxymethoxyphenyllithium for the synthesis of 4'- C -aryl-D-ribonucleoside analogue [19]. Starting from the platform molecule 64 , addition of an excess of phenylmagnesium bromide at 10 °C afforded two isomeric lactones 70 and 71 in 81% yield.…”

Section: Addition Of An Aromatic Ring To a Carbonyl Groupmentioning

confidence: 99%

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Synthesis of C-Arylnucleoside Analogues

Len

Enderlin

2015

Molecules

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“…[7]) to prepare it from the oxime of the erythruronolactone 3 [8] failed. Concerning the stability of such nitrolactones CJ [9].…”

mentioning

confidence: 98%

Deoxy‐nitrosugars, 7th communication Synthesis of methyl shikimate and of diethyl phosphashikimate from D‐ribose

Mirza

Vasella

1984

Helvetica Chimica Acta

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SummaryThe chain elongation of the deoxy-nitroribose 6 by a Michael addition to the vinylphosphonate 7 followed by a solvolysis gave the heptulosephosphonate 11 (87 %). From 11, the key intermediates 15 and 16 (77%) were obtained by a highly diastereoselective reduction, followed by detritylation, periodate cleavage, and silylation. Methoxycarbonylation of 15 and 16 gave 17 and 18 which were converted into methyl shikimate (21 ; 79 %) by intramolecular olefination and partial deprotection. Similarly, phosphonoylation of 16 gave 22 (99%) which was transformed into the diethyl phosphashikimate 2 (53% from 6).The importance of shikimic acid (1) as a biosynthetic intermediate is well recognized [2], and several syntheses of 1 including three enantiospecific ones [3][4][5] have been reported. In all these enantiospecific syntheses carbohydrates have been used as starting material and, the problem of chain extension and of the formation of cyclohexenes from carbohydrates had to be solved. We have proposed a solution to the problem of chain elongation using 1-deoxy-1-nitroaldoses [6]. The synthesis of 1 and of the corresponding phosphashikimic acid derivative 2 allows to extend the scope of this method and to look further at the synthesis of carbocycles from carbohydrates (cf.[5]). OH 1 OH 2We had planned to first extend the chain of a 1-deoxy-1-nitro sugar*) by a Michael addition to the vinylphosphonate 5 [ 101 (Scheme), then generate an aldehydophosphonate, and finally cyclize this intermediate by an intramolecular olefination. I) 6th Communication: [l].We had intended to use the nitro sugar 4, but the attempts (cf. [7]) to prepare it from the oxime of the erythruronolactone 3 [8] failed. Concerning the stability of such nitrolactones CJ [9].

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L‐Erythruronic Acid Derivatives as Building Blocks for Nucleoside Analogs. Synthesis of 4′‐C‐Aryl‐D‐ribonucleosides

Cited by 28 publications

References 29 publications

Synthesis of a Bifunctional Ligand for the Sequential Enantioselective Catalysis of Various Reactions

Synthesis of a Bifunctional Ligand for the Sequential Enantioselective Catalysis of Various Reactions

Synthesis of C-Arylnucleoside Analogues

Deoxy‐nitrosugars, 7th communication Synthesis of methyl shikimate and of diethyl phosphashikimate from D‐ribose

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