SYNTHESIS OF 2S,5S-AND 2R,5S-5-HYDROXYPIPECOLIC ACID VIA AMIDE-METHYLENATION OF S-5-HYDROXY-2-PIPERIDONE WITH DIMETHYLTITANOCENE

被引：39
作者：
HERDEIS, C
HELLER, E
机构：
[1] Institut für Pharmazie und Lebensmittelchemie der Universität 8700 Würzburg, Am Hubland
来源：
TETRAHEDRON-ASYMMETRY | 1993年 / 4卷 / 09期
关键词：
D O I：
10.1016/S0957-4166(00)82257-0
中图分类号：
O61 [无机化学];
学科分类号：
070301 ; 081704 ;
摘要：
A route to 2S,5S-and 2R,5S-hydroxypipecolic acid is presented, starting with the enantiopure 5S-5-hydroxy-piperidone 7. The key step of this reaction sequence is the chemoselective methylenation of the amide carbonyl group of 8 with dimethyltitanocene 9 to 10. The transformation of the exocyclic enecarbamate double bond to the carboxylic acid group is best accomplished via hydroboration/oxidation to the alcohol 11a,b. Separation and oxidation of the diastereomers 11a,b, to 14a, and 14b, and hydrolysis furnishes the diastereomeric pipecolic acids 15a and 15b in enantiopure form.
引用
收藏
页码：2085 / 2094
页数：10
相关论文
共 34 条
[1]   STEREOSELECTIVE SYNTHESIS OF SUBSTITUTED PIPECOLIC ACIDS [J].
ANGLE, SR ;
ARNAIZ, DO .
TETRAHEDRON LETTERS, 1989, 30 (05) :515-518
[2]  
ANGST C, 1989, J MED CHEM, V32, P2171
[3]   CHIRAL SYNTHESIS OF 5-HYDROXY-(L)-PIPECOLIC ACIDS FROM (L)-GLUTAMIC ACID [J].
BAILEY, PD ;
BRYANS, JS .
TETRAHEDRON LETTERS, 1988, 29 (18) :2231-2234
[4]   ASYMMETRIC-SYNTHESIS OF PIPECOLIC ACID-DERIVATIVES USING THE AZA-DIELS-ALDER REACTION [J].
BAILEY, PD ;
BROWN, GR ;
KORBER, F ;
REED, A ;
WILSON, RD .
TETRAHEDRON-ASYMMETRY, 1991, 2 (12) :1263-1282
[5]   A DIRECT SYNTHESIS OF DL-BAIKIAIN [J].
BURGSTAHLER, AW ;
AIMAN, CE .
JOURNAL OF ORGANIC CHEMISTRY, 1960, 25 (04) :489-492
[6]  
CLAUSS K, 1962, LIEBIGS ANN CHEM, V654, P8
[7]   SUBSTITUTION OF PROLINE WITH PIPECOLIC ACID AT THE SCISSILE BOND CONVERTS A PEPTIDE SUBSTRATE OF HIV PROTEINASE INTO A SELECTIVE INHIBITOR [J].
COPELAND, TD ;
WONDRAK, EM ;
TOZSER, J ;
ROBERTS, MM ;
OROSZLAN, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 169 (01) :310-314
[8]  
COUTY F, 1990, SYNLETT, P731
[9]  
DOBSON A, 1958, J CHEM SOC, P3642
[10]   TOTAL SYNTHESIS OF DL-ANTIBIOTIC 593A [J].
FUKUYAMA, T ;
FRANK, RK ;
JEWELL, CF .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (06) :2122-2123
1234