Stereoselective Total Synthesis of (-)-Ovalicin

Abstract

A new synthetic route for epoxyketone 3 is described, which is a key intermediate in Barton's synthesis of ovalicin (1), a powerful anti-angiogenetic inhibitor, from commercially available D-ribose. The key reactions involved in this synthesis are ring-closing metathesis, Rubottom oxidation and Corey-Chaykovsky epoxidation. The subsequent transformations are carried out according to Barton's strategy to complete the total synthesis of (-)-ovalicin.

Cycloalkenyl Halide Substitution Reactions of Enantiopure Arene cis‐Tetrahydrodiols with Boron, Nitrogen and Phosphorus Nucleophiles

“…The solvent was removed under vacuum and the residue purified by flash chromatography (EtOAc‐hexane, 2:1→EtOAc) to furnish the title compound 10 as a clear oil, yield: 77 mg (57%). The spectroscopic data of compound 10 were in good agreement with the literature data 36. [ α ] D : + 58.4 ( c 0.51, CHCl 3 ), lit36 [ α ] D ( ent ): −63.2 ( c 1.0, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): δ =4.54–4.56 (1 H, m), 4.22 (1 H, d, J =5.4 Hz), 2.41–2.47 (1 H, m), 2.13–2.27 (2 H, m), 1.84–1.93 (3 H, m), 1.38 (3 H, s), 1.33 (3 H, s).…”

“…Employing Verkade’s general procedure31 cycloalkenyl bromide 3d , on reaction with piperidine, yielded the known enantiopure ketone 10 via the transient enamine intermediate 3n ,36 during an attempted purification of the reaction product by flash chromatography. Acetonide 10 is a configurationally stable form of the stereochemically labile diol 11 37 which is a keto‐tautomer of cis ‐tetrahydrophenol 12 .…”

“…The spectroscopic data of compound 10 were in good agreement with the literature data. [36] [a] D : + 58.4 (c 0.51, CHCl 3 ), lit [36] [a] D (ent): À63. A C H T U N G T R E N N U N G (3aS,7aS)-7-(Diphenylphosphinoyl)-2,2-dimethyl3a,4,5,7a-tetrahydrobenzoA C H T U N G T R E N N U N G [1,3]dioxole (13) A C H T U N G T R E N N U N G (1S,2S)-1,2-Isopropylidenedioxy-3-bromocyclohex-3-ene 3d (1.5 g, 6.4 mmol), Pd 2 A C H T U N G T R E N N U N G (dba) 3 …”

Computer Modelling and Synthesis of Deoxy and Monohydroxy Analogues of a Ribitylaminouracil Bacterial Metabolite that Potently Activates Human T Cells

“…Methyl 2,3‐ O ‐isopropylidene‐5‐deoxy‐β‐ d ‐ribofuranoside (33) : Step 1 : Following a modified literature procedure, 2,2‐dimethoxypropane (30 mL) was added to a suspension of d ‐ribose ( 24 , 12.26 g, 81.7 mmol) in acetone and methanol (120 mL, 2:1, anhydrous). After cooling to 0 °C, HCl (4 m in dioxane, 6 mL) was added dropwise.…”

“…After adding two drops of 5% HCl in methanol, the mixture was stirred for an additional 24 h. The mixture was concentrated to give the desired amine 32 as ay ellow oil, which was used without further purification. 1 Step 1: Following am odified literature procedure, [30] 2,2-dimethoxypropane (30 mL) was added to as uspension of d-ribose (24, 12.26 g, 81.7 mmol) in acetone and methanol (120 mL, 2:1, anhydrous). After cooling to 0 8C, HCl (4 m in dioxane, 6mL) was added dropwise.…”