Solution-phase parallel synthesis of novel spirooxazolinoisoxazolines.
A practical and efficient solution-phase parallel synthesis of spirooxazolinoisoxazolines has been developed. Starting from methyl serine ester, the key steps are (1) acylation with concomitant beta-elimination to form an alpha,beta-unsaturated ester, (2) 1,3-dipolar cycloaddition with an oxime to form an isoxazoline ring, (3) reduction with NaBH(4), and (4) mesylation and in situ cyclization to form an oxazoline ring. All reaction steps and workup procedures were modified to allow the use of automated equipment including a synthesizer, a multifunctional liquid handler, and a vacuum centrifuge. Using this equipment, we synthesized a 100-membered library of spirooxazolinoisoxazoline in high yield, high purity, and excellent regioselectivity.
Shih
Hao-Wei
HW
The Genomics Research Center, Academia Sinica, No 128, Academia Road Sec 2, Nankang District, Taipei 11529, Taiwan.
Guo
Chih-Wei
CW
Lo
Kien-Hock
KH
Huang
Min-Yang
MY
Cheng
Wei-Chieh
WC
D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D010080:Oxazoles; D012996:Solutions; D013141:Spiro Compounds