De Novo Asymmetric Synthesis of Fridamycin E

Abstract

A de novo asymmetric synthesis of (R)- and (S)-fridamycin E has been achieved. The entirely linear route required only nine steps from commercially available starting materials (16% overall yield). Key transformations included a Claisen rearrangement, a Sharpless dihydroxylation and a cobalt-catalyzed epoxide carbonylation to give a β-lactone intermediate. Antibacterial activities were determined for both enantiomers using two strains of E. coli, with the natural (R)-enantiomer showing significant inhibition against a Gram-(+)-like imp strain (MIC = 8 μM).

Cobalt‐Catalyzed ortho‐Methylation of Ferrocenes Bearing ortho‐Directing Groups by Catalytic Directed C–H Bond Activation

“…Bipyridyl and both sterically hindered (mesityl, SIMes) or more flexible (isopropyl, SIiPr) NHC ligands [10] (Entries 10-12) gave only traces or poor yields of rac-2, indicating that a diamine ligand is superior. DMPU had successfully been used as a co-solvent [49,55] or solvent [45,56] in Co-catalyzed C-H functionalizations, but here the yields were only slightly improved (Entries 16, 17), although the dimethylation to 3 could remarkably be reduced to only 5 %, when DMPU was used as a co-solvent (Entry 16). The reaction in DMPU was carried out at 60 and at 100°C, both conditions giving the same yield (Entry 17).…”

Total Synthesis of Aquayamycin

“…However,a fter extensive effort, introduction of allyl group wasa chieved via the naphthoquinone 10.T hus, after treatment of 24 with CAN, the resulting naphthoquinone 10 was added to as olution of allylindium species, which was prepared in situ from indium, sodiumi odide, and allylbromide, [14] to form the allylated quinone 25.T hen, one-pot rearrangement-methylationo f25 was conducted using NaH and MeOTst oa fford 26 in 76 %y ield in 2s teps. [21,22] Next, allylnaphthalene 26 was converted into ketoaldehyde 9 by removal of the TBS group, followed by Dess-Martin oxidation and mild oxidative cleavage using OsO 4 , NaIO 4 ,a nd 2,6-lutidine. [23] Next, intramolecularp inacol coupling of ketoaldehyde 9 was examined utilizing aP edersen modified procedure.…”

Convergent de novo synthesis of vineomycinone B2 methyl ester

“…Herein we describe our successful approach to vineomycinone B 2 methyl ester, which is based upon our de novo Achmatowicz approach to carbohydrates 6 and our successful syntheses of fridamycin E 8 from achiral starting materials (acyl furan and anthrarufin, respectively). We believe this convergent de novo asymmetric approach that utilizes a late stage Suzuki’s glycosylation to install the β - C -glycoside provides synthetic material in a more efficient manner than the previous routes.…”

“…Building upon our fridamycin E work, we imagined an aglycon subunit suitable for coupling (e.g., 3 ) could be prepared from commercially available anthrarufin 5 . 8 …”