# Exploiting Unconventional Building Blocks in Chemical Synthesis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $582,296

## Abstract

Project Summary/Abstract
 The central objective of this application is to harness unconventional synthetic
building blocks for the development of new, reliable, and efficient, methodologies.
These methodologies are intended to enable the construction of stereochemically rich
scaffolds, including those seen in naturally occurring small molecules and medicines.
The development of new methods and the syntheses of complex small molecules
continues to be vital areas of research. Most medicinal agents on the market are
prepared by organic synthesis, including the large majority of all new drugs that have
become available over the past three decades. The chemical structures of new drug
entities are becoming increasingly complex, now often bearing sp3 centers rather than
“flat” structures. This has led to an increased need for chemists to develop new
methods that can reliably build intricate structures.
 The two unconventional building blocks we seek to harness in the proposed
studies are amides and strained cyclic alkynes and allenes. Regarding amides, the C–N
bond of amides has long been viewed as stable, such that synthetic methodologies that
rely on C–N bond cleavage have remained limited. We seek to develop methods that
utilize nickel catalysis to harness amide functional groups as synthons. We propose to
assemble important linkages with defined stereocenters, including quaternary
stereocenters, using catalysis and chemoenzymatic methods. These efforts provide
new opportunities in the area of strong bond activation by nickel catalysis, along with
new tools for the manipulation of amides via C–N bond cleavage. With regard to
strained cyclic alkynes and allenes, we seek to intercept these transient, highly reactive
species to efficiently build complex molecular scaffolds. Such methods should allow for
the establishment of scaffolds bearing two new bonds and three sp3 centers.
Enantiospecific and catalytic enantioselective variants will be targeted. Our
methodologies will be evaluated in the context of several synthetic endeavors. The
results of our studies should lead to powerful new strategies and tools for accessing
various molecules of importance, including natural products and medicines.

## Key facts

- **NIH application ID:** 10766254
- **Project number:** 5R35GM139593-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Neil K. Garg
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $582,296
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766254

## Citation

> US National Institutes of Health, RePORTER application 10766254, Exploiting Unconventional Building Blocks in Chemical Synthesis (5R35GM139593-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10766254. Licensed CC0.

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