title: Stereochemical elucidation and total synthesis of dihydropacidamycin D, a semisynthetic pacidamycin.
abstract: 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.
authors.affiliation: Microcide Pharmaceuticals, Inc., 850 Maude Avenue, Mountain View, California 94043, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Boojamra
authors.forename: R C
authors.initials: RC
authors.lastname: Lemoine
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Léger
authors.forename: K A
authors.initials: KA
authors.lastname: Stein
authors.forename: N G
authors.initials: NG
authors.lastname: Vernier
authors.forename: A
authors.initials: A
authors.lastname: Magon
authors.forename: O
authors.initials: O
authors.lastname: Lomovskaya
authors.forename: P K
authors.initials: PK
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Chamberland
authors.forename: M D
authors.initials: MD
authors.lastname: Lee
authors.forename: S J
authors.initials: SJ
authors.lastname: Hecker
authors.forename: V J
authors.initials: VJ
authors.lastname: Lee
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010455:Peptides; D011741:Pyrimidine Nucleosides; C432124:dihydropacidamycin D