Investigation of a route to ibotenic acid analogues via a reduced pyroglutamate template

Abstract

Two alternative "ring switch" based syntheses have been shown to give access to the reduced protected homochiral analogues, 27, 28 and 36, of the CNS active compound ibotenic acid.

Synthesis of condensed pyridones by using a new ring switching reaction

“…Other pyridones act as HIV-1 reverse transcriptase inhibitors [7], or as herbicides [8], insecticides [9], fungicides [10], antiviral [7,11], or antioxidant agents [12] (Figure 1 The ring-switching reaction [13] represents a special type of ring transformation where a ring and a chain moiety in the adduct are transferred to each other giving the product [14]. Often a bisnucleophile reacts with a biselectrophile [15], and when a derivative of pyroglutamic acid is utilized, the reaction yields peptidomimetic compounds as illustrated in Scheme 1 [16].…”

Synthesis and Transformations of Novel L‐Phenylalanine Derived Pyrazolidin‐3‐ones

“…Nonracemic pyrazolidinones have been prepared from enantiomerically pure 2,3‐disubstituted oxirane carboxylic acids . Ring switching methodology was used to prepare optically active diastereoizomeric pyrazolidin‐3‐ones …”

“…[42][43][44] To the best of our knowledge, we could find no chiral nonracemic C(5)-substituted pyrazolidin-3-one diastereoisomers of type A prepared from chiral pool amino acid derivatives (Scheme 1). A literature search for compounds of type A revealed pyrazolidin-3-ones with alanine 43 and serine 42,44 side chain residue (R) and a non-proteinogenic side chain (R = CO 2 R) 45 . This prompted us to investigate the preparation of pyrazolidin-3-ones of type A starting from N-Cbz-protected L-phenylalanine as a model amino acid via the corresponding keto ester, and cyclization with hydrazines in the final step.…”