Synthesis of Optically Pure 3,4-Disubstituted l-Glutamates from a Novel 2,3-Aziridino-γ-lactone 4-Carboxylate Derivative

Abstract

The synthesis of the N-acetyl and N-Cbz derivatives of (1S,4S,5R)-4-(methoxycarbonyl)-3-oxa-6-azabicyclo[3.1.0]hexan-2-one (24 and 27, respectively) from d-ribose is described. While compound 24 reacted with methanol in the presence of boron trifluoride etherate to give the novel 2,3-iminoglutamate derivative 28, compound 27 afforded, under the same conditions, the 4(S)-hydroxy-3(S)-methoxy-l-glutamate 31. Similarly, reaction of 27 with ethanol and benzyl alcohol gave the corresponding 3(S)-ethoxy and 3(S)-(benzyloxy) analogues of 31. This represents the first example of the use of a carbohydrate for the preparation of l-glutamate derivatives as well as the first example of a stereocontrolled synthesis of glutamate analogues dissymmetrically substituted at the β,γ-positions.

Synthesis of 3,4‐Fused Bicyclic β‐Lactams and Their Transformation into Methyl cis‐3‐Aminotetrahydrofuran‐2‐carboxylates

“…Due to the high stereoselectivity in the Staudinger synthesis of cis ‐β‐lactams 4 and transfer of this relative configuration through the reaction sequence, cis ‐3‐aminotetrahydrofuran‐2‐carboxylates 7 were deduced as the final reaction products. Moreover, the experimental coupling constants between the protons at C‐2 and C‐3 in tetrahydrofurans 7 (6.2–8.3 Hz, CDCl 3 ) are in accordance with coupling constants of similar compounds described in the literature 36,37. Nonetheless, coupling constants of 4.6–4.8 Hz between the protons at C‐2 and C‐3 have also been reported for cis ‐3‐azidotetrahydrofuran‐2‐carboxylates, making a conclusive stereochemical assignment solely based on coupling constants precarious 38…”

ChemInform Abstract: Synthesis of 3,4‐Fused Bicyclic β‐Lactams and Their Transformation into Methyl cis‐3‐Aminotetrahydrofuran‐2‐carboxylates.

“…Thus, the synthesis of the desired 3-aminotetrahydrofuran-2-carboxylates 7a-e was accomplished through ring opening of bicyclic cis-βlactams 6a-e by means of HCl in methanol. [36,37] Nonetheless, coupling constants of 4.6- 4.8 Hz between the protons at C-2 and C-3 have also been reported for cis-3-azidotetrahydrofuran-2-carboxylates, making a conclusive stereochemical assignment solely based on coupling constants precarious. Treatment of β-lactam 6d with 4 or 8 equiv.…”

“…Moreover, the experimental coupling constants between the protons at C-2 and C-3 in tetrahydrofurans 7 (6.2-8.3 Hz, CDCl 3 ) are in accordance with coupling constants of similar compounds described in the literature. [36,37] Nonetheless, coupling constants of 4.6- 4.8 Hz between the protons at C-2 and C-3 have also been reported for cis-3-azidotetrahydrofuran-2-carboxylates, making a conclusive stereochemical assignment solely based on coupling constants precarious. [38] Subsequently, NOESY experiments were performed on 3-aminotetrahydrofuran-2-carboxylates 7.…”

Exploring human adenosine A3 receptor complementarity and activity for adenosine analogues modified in the ribose and purine moiety

“…41 Periodate oxidation 46 followed by esterification of the carboxylic acid and subsequent treatment with methylamine in a pressure tube 47 afforded the ribofuronamides 17 40 and 18. A one-pot deprotection-acetylation strategy afforded the peracylated sugar moieties 19 and 20 modified at the 3′,5′-positions.…”