# A Modular and Scalable Route to Protected Cyclopropane Amino Acid Building Blocks

## TL;DR

This paper presents a new, safer method to create cyclopropane amino acids using common reagents and avoiding toxic or expensive materials.

## Contribution

The novel contribution is an improved, scalable synthesis route for cyclopropane amino acids without neurotoxic or precious metal reagents.

## Key findings

- Bicyclic carbamates were synthesized enantioenriched and diastereopure via Hofmann rearrangement.
- Cyclopropane amino acids were obtained through ring-opening and further functionalized via oxidation and SN2 pathways.
- The amino acids were successfully incorporated into peptides using solid-phase peptide synthesis.

## Abstract

An improved method for the synthesis of noncanonical
cyclopropane
amino acids from common laboratory reagents is described, avoiding
the use of neurotoxic oxidants or precious metal catalysts. Intramolecular
isocyanate trapping via a Hofmann rearrangement permits the synthesis
of bicyclic carbamates in an enantioenriched and diastereopure manner.
Subsequent ring-opening of these species allows access to cyclopropane
amino acids which can be further functionalized via oxidation and
SN2 pathways and incorporated into peptides via solid-phase
peptide synthesis.