Total asymmetric synthesis of (-)-Phenylhistine, (-)-Aurantiamine and related compounds. Part I.
A new general, short, and efficient strategy for the construction of dehydro-diketopiperazines was developed. Horner-Emmons type coupling between a phosphinyl glycine ester and a formyl heterocycle is the key coupling reaction, which proceeds in good-to-excellent yields on several sterically-hindered substrates. Moreover, racemization of the parent L-amino acids is avoided as a result of the mild basic conditions used. The selection of the NH protective group of the formyl heterocycle was crucial. N-tosylated heterocycles proved ideal for this reaction sequence. Thus, the title compounds, (-)-Phenylhistine and (-)-Aurantiamine, were prepared in high yield (four steps, 47% overall) and optical purity. Furthermore, the synthesis of unnatural derivatives including an indole analogue was successfully completed.
Couladouros
Elias A
EA
Chemistry Laboratories, Agricultural University of Athens, Iera Odos 75, Athens 118 55, Greece. ecoula@chem.demokritos.gr
Magos
Alexandros D
AD
D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism
D007202:Indicators and Reagents; D010879:Piperazines; C418737:aurantiamine