Enantioselective Syntheses of (R)‐Amino Acids Using L‐Valine as Chiral Agent

Abstract

(R)‐Amino Acids can be synthesized via the cyclic bislactim ethers (dihydropyrazines) of cyclo‐(L‐Val‐Gly), by successive metalation, alkylation, and hydrolysis, in good yields and in high optical purity. They are e.g. of importance as enzyme inhibitors. Presumably the reaction proceeds via the planar dihydropyrazine anion (1).

Synthesis of Silaproline, a New Proline Surrogate

“…[11] However, in the particular case of -silaproline, the C α is of (R)-configuration due to changed atom priorities.…”

“…Deprotonation with BuLi of the bis-lactim ether 1, resulting from the -Val-Gly diketopiperazine, [11] afforded a planar cyclic anion intermediate which reacted with bis-(iodomethyl)dimethylsilane (2) to give compounds 3 and 4. Silane 2 was obtained from the corresponding dichloride Scheme 1.…”

“…One of the most versatile and prolific chiral glycine equivalents is Schöllkopf's bis-lactim ether derived from cyclo-(ValGly). [11] Although this method has been extensively used to prepare various nonnatural amino acids, [12] only one application concerns a silicon-containing amino acid, the trimethylsilylalanine (TMS-Ala) which is proposed as a substitute for phenylalanine. [13] In this case, TMS-Ala is prepared in both enantiomeric forms by asymmetric synthesis starting from Schöllkopf's reagent and chloromethyltrimethylsilane.…”

Asymmetric Synthesis of (S)‐(‐)‐Acromelobic Acid.

“…The bromide 3 finally should easily be available from citrazinic acid (4). The successful synthesis of (S)-(Ϫ)-acromelobic acid (1) described herein is based on the bis(lactim) ether method [6,17] and the introduction of an enol ether by the Stille coupling [18] of 2 and subsequent ozonolysis to the corresponding ester.…”

“…[17] Infrared (IR) spectra were obtained using a PerkinϪElmer 1600 spectrometer. 1 H and 13 C NMR spectra were obtained using a JEOL 400 GX JNM or a Bruker Advance DRX 600 spectrometer.…”