Thermal atropisomerism of aglucovancomycin derivatives:: Preparation of (M,M,M)- and (P,M,M)-aglucovancomycins

被引:53
作者
Boger, DL
Miyazaki, S
Loiseleur, O
Beresis, RT
Castle, SL
Wu, JH
Jin, Q
机构
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1021/ja981928i
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The degradation of vancomycin to a series of aglucovancomycin derivatives containing modifications in key functional groups and a study of their thermal atropisomerism are detailed. In all of the cases, selective isomerism of the DE ring system atropisomers was observed under conditions where the CD and AB stereochemistries were unaffected. Competitive retro aldol ring cleavage of the CD and DE ring systems (CD > DE) was observed but could be minimized by the choice of solvent and thermal conditions (DE ring system) or precluded by alcohol protection (CD ring system). Similarly, competitive main chain succinimide formation through the loss of ammonia from the Asn residue could be minimized by the choice of thermal conditions or prevented by carboxamide protection. Resynthesis of natural aglucovancomycin, (M,M,M)-2, and its unnatural DE atropisomer (P,M,III)-2 from 6 are described. The comparative antimicrobial activity of the key derivatives and their unnatural DE ring system P-diastereomers are disclosed.
引用
收藏
页码:8920 / 8926
页数:7
相关论文
共 33 条
  • [1] Thermal atropisomerism of fully functionalized vancomycin CD, DE, and CDE ring systems
    Boger, DL
    Loiseleur, O
    Castle, SL
    Beresis, RT
    Wu, JH
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (24) : 3199 - 3202
  • [2] Synthesis of the vancomycin CDE ring system
    Boger, DL
    Beresis, RT
    Loiseleur, O
    Wu, JH
    Castle, SL
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (07) : 721 - 724
  • [3] Synthesis of appropriately functionalized vancomycin CD and DE ring systems
    Boger, DL
    Borzilleri, RM
    Nukui, S
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (24) : 3091 - 3096
  • [4] Synthesis of the vancomycin CD and DE ring systems
    Boger, DL
    Borzilleri, RM
    Nukui, S
    Beresis, RT
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (14) : 4721 - 4736
  • [5] BOGER DL, IN PRESS J ORG CHEM
  • [6] Synthesis of model tricyclic C-O-D-O-E-F-O-G ring of teicoplanin
    BoisChoussy, M
    Vergne, C
    Neuville, L
    Beugelmans, R
    Zhu, JP
    [J]. TETRAHEDRON LETTERS, 1997, 38 (33) : 5795 - 5798
  • [7] Semisynthetic glycopeptide antibiotics
    Cooper, RDG
    Thompson, RC
    [J]. ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 31, 1996, 31 : 131 - 140
  • [8] Evans D.A., 1994, GLYCOPEPTIDE ANTIBIO, Vfirst, P63
  • [9] Synthesis and conformational properties of the M(4-6)(5-7) bicyclic tetrapeptide common to the vancomycin antibiotics
    Evans, DA
    Dinsmore, CJ
    Ratz, AM
    Evrard, DA
    Barrow, JC
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (14) : 3417 - 3418
  • [10] Approaches to the synthesis of the vancomycin antibiotics. Synthesis of orienticin C (bis-dechlorovancomycin) aglycon
    Evans, DA
    Barrow, JC
    Watson, PS
    Ratz, AM
    Dinsmore, CJ
    Evrard, DA
    DeVries, KM
    Ellman, JA
    Rychnovsky, SD
    Lacour, J
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (14) : 3419 - 3420