Desymmetrization of Cyclic Anhydrides Using Dihydroxy Compounds:  Selective Synthesis of Macrocyclic Tetralactones

Abstract

[reaction: see text] The desymmetrization of cyclic anhydrides is carried out using dihydroxy compounds. A mild route to synthesize fused saturated/unsaturated macrocyclic tetralactones with different ring sizes (20-34) having a wide variety of spacers is described. The structure is confirmed by the representative single-crystal X-ray analysis. The multiple reduction of unsaturated macrocyclic tetralactones is also illustrated. This method is mild, selective, and efficient and achieves high yield.

Hydrolytically Degradable PEG-Based Inverse Electron Demand Diels–Alder Click Hydrogels

“…CA was conjugated onto PEG terminal hydroxyl groups via esterification using DMAP as a catalyst. The CA underwent cyclic desymmetrization, yielding PEGNB CA , a functional macromer with the norbornene group and a carboxylic acid that can be utilized for additional functionalization (Figure a) . Successful synthesis of PEGNB CA and PEGTz/PEG-mTz permitted bio-orthogonal hydrogel cross-linking via the iEDDA click reaction (Figure c).…”

“…The CA underwent cyclic desymmetrization, yielding PEGNB CA , a functional macromer with the norbornene group and a carboxylic acid that can be utilized for additional functionalization ( Figure 1 a). 31 Successful synthesis of PEGNB CA and PEGTz/PEG-mTz permitted bio-orthogonal hydrogel cross-linking via the iEDDA click reaction ( Figure 1 c). Our previous work showed that thiol-norbornene photoclick hydrogels cross-linked by PEGNB degraded slowly owing to the slow ester hydrolysis kinetics.…”

Functional Polylactide-g-Paclitaxel–Poly(ethylene glycol) by Azide–Alkyne Click Chemistry

“…LA was recrystallized from dry EtOAc twice prior to use. α-Methyloxy-ω-carboxyl PEG was prepared by the esterification reaction of α-methyloxy PEG with an excess of glutatic anhydride in the presence of triethylamine in DCM . 2-Hydroxy-4-pentynoic acid was synthesized following a reference method .…”

“…R-Methyloxy-ω-carboxyl PEG was prepared by the esterification reaction of R-methyloxy PEG with an excess of glutatic anhydride in the presence of triethylamine in DCM. 48 2-Hydroxy-4-pentynoic acid was synthesized following a reference method. 14 4-(Dimethyleamino)pyridinium 4-toluenesulfonate (DPTS) was prepared from DMAP and PTSA based on a literature approach.…”

New Approach to the Synthesis of Macrocyclic Tetralactones via Ring-Closing Metathesis Using Grubbs' First-Generation Catalyst

“…Even though literature methods provide a mixture of dilactones and tetralactones, the reactions give low yields and require drastic conditions. Recently, we have reported the synthesis of macrocyclic tetralactones via DCC/DMAP cyclization of dicarboxylic acids. Since there has been no other literature report toward the synthesis of macrocyclic tetralactones, we herein report a successful method for macrocyclic tetralactones with different ring sizes via RCM reaction.…”