ChemInform Abstract: Improved Synthesis of Some 2‐Esters of N‐Protected L‐Glutamic Acid.

Abstract

Die im Titel genannten Verbindungen (IIa) und (IIb) werden auf dem gezeigten Weg ausgehend von (Ia) und (Ib) erhalten.

Quinazoline Antifolate Thymidylate Synthase Inhibitors: γ-Linked l-d, d-d, and d-l Dipeptide Analogues of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic Acid (ICI 198583),

“…These unexpected results led us to an investigation of the optical purity of the glutamate 60 which was used as one of the chiral building blocks for the preparation of both 64a,b. Indeed, the specific optical rotation of 60 was found to be +20.0°, significantly lower than that reported for the L-enantiomer (-26.6°), 28 suggesting that this compound was enantiomerically impure. As a consequence, quinazoline antifolates 64a,b were obtained as diastereoisomeric mixtures D-L/L-L and D-D/L-D, respectively.…”

“…29 Benzyl chloroformate was then used for the introduction of the Z-group 30 and the R-carboxyl of 58 masked as its tert-butyl ester by treatment with Bu t OH/POCl 3 /pyridine. 28 In the last step, the γ-methyl ester was hydrolyzed under alkaline conditions to afford 60 in 33% overall yield. 31…”

“…An analytically pure sample was obtained after purification by column chromatography using 5% MeOH in CHCl3 as eluent: mp 80-83 °C (lit. 28 ) +20.0°(c ) 1.2, MeOH) (lit. 28 [R] 20 ) -26.6°(c ) 1.2, MeOH) for the L-enantiomer).…”