Thiol-Ene Click-Inspired Late-Stage Modification of Long-Chain Polyurethane Dendrimers

The construction of well-defined polyurethane dendrimers is challenging due to the high reactivity of externally added or in situ formed isocyanates leading to the formation of side products. With a primary focus of dendrimer research being the interaction of the periphery and the core, we report the synthesis of a common polyurethane dendron, which allows for the late-stage variation of both the periphery and the core. The periphery can be varied simply by installing a clickable unit in the dendron and then attaching to the core and vice-versa. Thus, a common dendron allows for varying periphery and core in the final two steps. To accomplish this, a protecting group-free, one-pot multicomponent Curtius reaction was utilized to afford a robust and versatile AB2 type polyurethane dendron employing commercially available simple molecules: 5-hydroxyisophthalic acid, 11-bromoundecanol, and 4-penten-1-ol. Subsequent late-stage modifications of either dendrons or dendrimers via a thiol-ene click reaction gave surface-functionalized alternating aromatic-aliphatic polyurethane homodendrimers to generation-three (G3). The dendrons and the dendrimers were characterized by NMR, mass spectrometry, and FT-IR analysis. A bifunctional AB2 type dendritic monomer demonstrated this approach’s versatility that can either undergo a thiol-ene click or attachment to the core. This approach enables the incorporation of functionalities at the periphery and the core that may not withstand the dendrimer growth for the synthesis of polyurethane dendrimers and other dendritic macromolecules.

Thiol-Ene Click Inspired Late-Stage Modification of Long-Chain Polyurethane Dendrimers

Compared to the synthesis of polyurethane polymers, construction of well-defined polyurethane dendrimers is challenging due to the high reactivity of externally added or in-situ formed isocyanates leading to the formation of side products. For this reason, the synthesis of dendritic polyurethanes is limited to very few reports. With primary focus of dendrimer research on the interaction of the periphery and the core, we report the synthesis of a common polyurethane dendron, which allows for late-stage variation of both the periphery and the core. The periphery can be varied simply by installing a clickable unit in the dendron and then attaching to the core and vice-versa. Thus, a common dendron allows for varying periphery and core in just two steps. To accomplish this, protecting group free one-pot multicomponent Curtius reaction was utilized to afford a robust and versatile AB2 type polyurethane dendron employing commercially available simple molecules 5-hydroxyisophthalic acid, 11-bromoundecanol, and 4- penten-1-ol. Subsequent late-stage modification of either dendrons or dendrimers via thiol-ene click reaction gave surface?functionalized alternating aromatic-aliphatic polyurethane homodendrimers to generation-three (G3). The dendrons and the dendrimers were characterized by NMR, mass spectrometry, and FT-IR analysis. A bifunctional AB2 type dendritic monomer demonstrated this approach's versatility that can either undergo a thiol-one click or attachment to the core. This approach enables the incorporation of functionalities at the periphery and the core that may not withstand the dendrimer growth for the synthesis of polyurethane dendrimers and other dendritic macromolecules

Thiol-Ene Click Inspired Late-Stage Modification of Long-Chain Polyurethane Dendrimers

Compared to the synthesis of polyurethane polymers, construction of well-defined polyurethane dendrimers is challenging due to the high reactivity of externally added or in-situ formed isocyanates leading to the formation of side products. For this reason, the synthesis of dendritic polyurethanes is limited to very few reports. With primary focus of dendrimer research on the interaction of the periphery and the core, we report the synthesis of a common polyurethane dendron, which allows for late-stage variation of both the periphery and the core. The periphery can be varied simply by installing a clickable unit in the dendron and then attaching to the core and vice-versa. Thus, a common dendron allows for varying periphery and core in just two steps. To accomplish this, protecting group free one-pot multicomponent Curtius reaction was utilized to afford a robust and versatile AB2 type polyurethane dendron employing commercially available simple molecules 5-hydroxyisophthalic acid, 11-bromoundecanol, and 4- penten-1-ol. Subsequent late-stage modification of either dendrons or dendrimers via thiol-ene click reaction gave surface?functionalized alternating aromatic-aliphatic polyurethane homodendrimers to generation-three (G3). The dendrons and the dendrimers were characterized by NMR, mass spectrometry, and FT-IR analysis. A bifunctional AB2 type dendritic monomer demonstrated this approach's versatility that can either undergo a thiol-one click or attachment to the core. This approach enables the incorporation of functionalities at the periphery and the core that may not withstand the dendrimer growth for the synthesis of polyurethane dendrimers and other dendritic macromolecules

A Model for Late-Stage Modification of Polyurethane Dendrimers Using Thiol-Ene Click Chemistry

Protecting group free, one-pot multicomponent Curtius reaction was utilized to afford diurethane G-1 dendron. In our synthetic approach, G-1 dendron can undergo late-stage modification using thiol-ene click reaction, which was then attached to the core to furnish a dendrimer. In another approach, the G-1 dendron was attached to the core and so formed dendrimer was surface functionalized using thiol-ene click chemistry. Either way, we can synthesize the dendrimer.

A Model for Late-Stage Modification of Polyurethane Dendrimers Using Thiol-Ene Click Chemistry

Protecting group free, one-pot multicomponent Curtius reaction was utilized to afford diurethane G-1 dendron. In our synthetic approach, G-1 dendron can undergo late-stage modification using thiol-ene click reaction, which was then attached to the core to furnish a dendrimer. In another approach, the G-1 dendron was attached to the core and so formed dendrimer was surface functionalized using thiol-ene click chemistry. Either way, we can synthesize the dendrimer.

Stereoselective Synthesis of Oxazolidin-2-ones via an Asymmetric Aldol/Curtius Reaction: Concise Total Synthesis of (−)-Cytoxazone

Herein, we are reporting an efficient approach toward the synthesis of 4,5-disubstituted oxazolidin-2-one scaffolds. The developed approach is based on a combination of an asymmetric aldol and a modified Curtius protocol, which uses an effective intramolecular ring closure to rapidly access a range of oxazolidin-2-one building blocks. This strategy also permits a straightforward and concise asymmetric total synthesis of (−)-cytoxazone. Consisting of three steps, this is one of the shortest syntheses reported to date. Ultimately, this convenient platform would provide a promising method for the early phases of drug discovery.

A Facile Synthetic Approach to Nonracemic Substituted Pyrrolo-allocolchicinoids Starting from Natural Colchicine

A six-step semisynthetic approach towards chiral nonracemic pyrrolo-allocolchicinoids starting from naturally occurring colchicine was developed. The synthetic scheme includes an electrocyclic tropolone ring contraction to afford allocolchicinic acid followed by the Curtius reaction, giving the corresponding aniline. The Sandmeyer reaction and copper-mediated hydrazination gave hydrazine-substituted allocolchicine. This was introduced into the Fischer indole synthesis, affording libraries of regioisomeric indole-based allocolchicine congeners.

The Curtius rearrangement: mechanistic insight and recent applications in natural product syntheses

An extensive review on the Curtius reaction and its recent applications in the synthesis of bioactive natural products are reported.