Synthesis of Z-5-Carboxymethylene-1,3-dioxolan-4-ones:  A Better Way

Abstract

The title compounds were prepared by a straightforward two-step procedure. Tartaric acid was first protected as either a bis(ketal) or a bis(acetal). This intermediate was then treated with potassium tert-butoxide at reduced temperature to effect a stereoselective elimination leading to the Z diastereomer of the alpha,beta-unsaturated acid. This protocol is useful for the laboratory-scale synthesis of these compounds but can also be scaled up to produce kilogram quantities of the material.

HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis

“…Most compounds were amide-diketo acids ( 7 – 40 , class I, Figure S1) and were conveniently prepared from the synthon ( Z )-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-one 17 by amine coupling. Among these compounds, 7 (Chart I) inhibited CrtM with IC 50 ~24 μM, K i ~ 250 nM (for comparison, K i of 3 ~ 70 nM 7 ), and blocked staphyloxanthin pigment formation (IC 50 = 4 μM).…”

“…We thus made a small screening library (38 compounds) of IN inhibitor-inspired molecules and their structures, and inhibition of S. aureus CrtM, E. coli UPPS, and S. aureus UPPS are shown in Figure S1 in the Supporting Information. Most compounds were amide-diketo acids ( 7 – 40 , class I, Figure S1 in the Supporting Information) and were conveniently prepared from the synthon ( Z )-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-one by amine coupling. Among these compounds, 7 (Chart ) inhibited CrtM with IC 50 ∼ 24 μM, K i ∼ 250 nM (for comparison, K i of 3 ∼ 70 nM) and blocked staphyloxanthin pigment formation (IC 50 = 4 μM).…”