CRYPTIC STEREOCHEMISTRY OF BERBERINE ALKALOID BIOSYNTHESIS

被引:34
作者
BJORKLUND, JA
FRENZEL, T
RUEFFER, M
KOBAYASHI, M
MOCEK, U
FOX, C
BEALE, JM
GROGER, S
ZENK, MH
FLOSS, HG
机构
[1] UNIV WASHINGTON,DEPT CHEM,SEATTLE,WA 98195
[2] OHIO STATE UNIV,DEPT CHEM,COLUMBUS,OH 43210
[3] UNIV MUNICH,LEHRSTUHL PHARMAZEUT BIOL,D-80333 MUNICH,GERMANY
关键词
D O I
10.1021/ja00110a009
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The cryptic stereochemistry of one-carbon transformations in berberine biosynthesis has been elucidated by the chiral methyl group methodology and tritium NMR spectroscopy. The transfer of the methyl group of AdoMet to oxygen and nitrogen occurs with complete inversion of configuration. The oxidative formation of the berberine bridge from the N-methyl group of reticuline involves removal of a methyl hydrogen with a primary kinetic isotope effect k(H)/k(D) = 4.0 and its replacement by the phenyl group in an inversion mode. The subsequent aromatization catalyzed by (S)-tetrahydroprotoberberine oxidase (STOX) involves nonstereospecific hydrogen removal from C-8 with little or no isotope effect. In the formation of the methylenedioxy bridge, a hydrogen is removed from the methoxy group with k(H)/k(D) > 5 and replaced by the adjacent phenolic oxygen with apparent retention, accompanied by substantial racemization. The subsequent reductive opening of the methylenedioxy bridge of berberine to the methoxy group of jatrorrhizine proceeds stereospecifically, apparently in an inversion mode. Mechanistic interpretations of these findings are discussed.
引用
收藏
页码:1533 / 1545
页数:13
相关论文
共 58 条
[1]   (S)-TETRAHYDROPROTOBERBERINE OXIDASE THE FINAL ENZYME IN PROTOBERBERINE BIOSYNTHESIS [J].
AMANN, M ;
NAGAKURA, N ;
ZENK, MH .
TETRAHEDRON LETTERS, 1984, 25 (09) :953-954
[2]   PURIFICATION AND PROPERTIES OF (S)-TETRAHYDROPROTOBERBERINE OXIDASE FROM SUSPENSION-CULTURED CELLS OF BERBERIS-WILSONIAE [J].
AMANN, M ;
NAGAKURA, N ;
ZENK, MH .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1988, 175 (01) :17-25
[3]   PREPARATION AND USE OF LIET3BT AND LIALT4 AT MAXIMUM SPECIFIC ACTIVITY [J].
ANDRES, H ;
MORIMOTO, H ;
WILLIAMS, PG .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1990, (08) :627-628
[4]  
Arigoni D., 1978, CIBA FDN S, P243
[5]   THE BIOSYNTHESIS OF PENICILLINS AND CEPHALOSPORINS [J].
BALDWIN, JE ;
ABRAHAM, E .
NATURAL PRODUCT REPORTS, 1988, 5 (02) :129-145
[6]   THE ROLE OF ALPHA-KETOGLUTARATE IN CEPHALOSPORIN BIOSYNTHESIS [J].
BALDWIN, JE ;
ADLINGTON, RM ;
SCHOFIELD, CJ ;
SOBEY, WJ ;
WOOD, ME .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1989, (15) :1012-1015
[7]   ISOPENICILLIN-N SYNTHASE - MECHANISTIC STUDIES [J].
BALDWIN, JE ;
BRADLEY, M .
CHEMICAL REVIEWS, 1990, 90 (07) :1079-1088
[8]  
BARTON DHR, 1963, P CHEM SOC LONDON, P267
[9]   PHENOL OXIDATION AND BIOSYNTHESIS .8. INVESTIGATIONS ON BIOSYNTHESIS OF BERBERINE AND PROTOPINE [J].
BARTON, DHR ;
HESSE, RH ;
KIRBY, GW .
JOURNAL OF THE CHEMICAL SOCIETY, 1965, (NOV) :6379-+
[10]   STEREOCHEMICAL COURSE OF THE KEY RING-FORMING REACTIONS IN CLAVULANIC ACID BIOSYNTHESIS [J].
BASAK, A ;
SALOWE, SP ;
TOWNSEND, CA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (04) :1654-1656