Stereochemical elucidation and total synthesis of dihydropacidamycin D, a semisynthetic pacidamycin.
Hydrogenation of the C(4') exocyclic olefin of the pacidamycins has been shown to produce a series of semisynthetic compounds, the dihydropacidamycins, with antimicrobial activity similar to that of the natural products. Elucidation of stereochemistry in the pacidamycins has been completed through a campaign of natural product degradation experiments in combination with the total synthesis of the lowest-molecular weight dihydropacidamycin, dihydropacidamycin D. The stereochemical identities of the tryptophan and two alanine residues contained in pacidamycin D have been shown to be of the natural (S) configuration, and the unique 3-methylamino-2-aminobutyric acid contained in this series of antibiotics has been shown to be of the (2S,3S) configuration. Finally, the stereochemistry obtained by hydrogenation of the C(4')-C(5') exocyclic olefin has been shown to be (R) at the C(4') nucleoside site.
Boojamra
C G
CG
Microcide Pharmaceuticals, Inc., 850 Maude Avenue, Mountain View, California 94043, USA.
Lemoine
R C
RC
Lee
J C
JC
Léger
R
R
Stein
K A
KA
Vernier
N G
NG
Magon
A
A
Lomovskaya
O
O
Martin
P K
PK
Chamberland
S
S
Lee
M D
MD
Hecker
S J
SJ
Lee
V J
VJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010455:Peptides; D011741:Pyrimidine Nucleosides; C432124:dihydropacidamycin D