A Short Synthesis of 4-Ketopipecolic Acid Hydrochloride

A Novel Approach for Mannich-Type Bases Having a Terminal Olefin: Zinc Triflate and Water-Promoted Cyclization/C−N Bond Cleavage Process

“…One of the most direct and powerful synthetic strategies for construction of them is the Mannich , or a very recently developed Mannich-type reaction which has broadened the potential usefulness of this widely known nucleophilic addition to aldimines . However, general preparation of pharmaceutically attractive β-aminoketones having a terminal olefin 1 by the reaction of aldimines with dienes bearing an enol ether moiety has not been reported yet because the [4 + 2] type cycloaddition generally proceeds to give cycloadducts 2 (Scheme ). , While the isolation of 1 has been reported, substituents of aldimines or dienes must be chosen carefully, , or a mixture of 1 and cycloadducts is obtained . In addition, other synthetic examples are complicated or not general, namely, (1) six steps from diethyl acetonylacetamidomalonate,5a (2) palladium(II)-assisted coupling process under severe temperature-controlled conditions, (3) hydrolysis of 6-vinyl-5,6-dihydro-4 H -1,3-oxazine which was formed by Diels−Alder reaction of 2-methoxy-1,3-butadiene with chloral acetylimine as a heterodiene .…”

Biosynthesis of Antibiotics of the Virginiamycin Family, 6. Biosynthesis of Virginiamycin S1

“…Removal of the ketal protecting group proved surprisingly difficult, but acid hydrolysis followed by ion-exchange chromatography yielded (R, 5)-4-oxopipecolic acid [2] as the hydrochloride in modest but unoptimized yield (Scheme 1). The synthetic material had identical spectroscopic properties (XH nmr) and tic mobility with a sample obtained by hydrolysis of virginiamycin Sv This procedure thus met our needs for 4-oxopipecolic acid [2], [After the completion of this work, an improved synthesis of 4-oxopipecolic acid was published (35).] The structural studies on virginiamycin Sj were carried out by hydrolysis of the antibiotic and by ion-exchange separation of the resulting amino acids (4).…”

Enantioselective Synthesis of (2R,4S)- and (2S,4R)-4-Hydroxypipecolic Acid from d-Glucoheptono-1,4-lactone

“…Such a hydroxy acid was oxidized to the 4-oxo- l -pipecolic acid, which was then reduced to (−)- 1 . The same 4-ketoacid has been also synthesized in racemic or chiral forms, and it was employed as intermediate in another synthesis of (−)- 1 from l -aspartic acid . Enzymatic or quinine resolution of racemic 1 led to the optically pure compound .…”