# Harnessing Strained Intermediates to Access Complex Molecules

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $184,995

## Abstract

Project Summary/Abstract
 The central objectives of this application are: (a) to develop new, reliable, and
efficient, methodologies that enable the construction of stereochemically rich scaffolds
and (b) to achieve the concise chemical syntheses of naturally occurring small
molecules that possess intricate chemical structures. The synthesis of complex small
molecules continues to be a vital area of research. In fact, 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. Additionally, it should be
emphasized that natural products serve as valuable leads for the ultimate discovery of
new medicines, in addition to inspiration for the development of new synthetic strategies
and methods. However, one of the key challenges we now face is uncovering reliable
means to construct ever more complex architectures, but with increased efficiency and
predictability.
 This proposal is focused on the development of methodology that will allow
chemists to harness transiently generated strained intermediates in order to efficiently
build complex molecular scaffolds. More specifically, we propose the use of uncommon
and highly reactive heterocyclic allenes to assemble complex architectures through the
introduction of up to two new bonds and three sp3 centers. Preliminary results
demonstrate the feasibility of the proposed methodologies, including enantiospecific and
catalytic enantioselective variants. In the final section, we propose a concise and
ambitious total synthesis of lissodendoric acid, a bioactive member of the manzamine
family of alkaloids that has yet to be synthesized. 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:** 10135289
- **Project number:** 3R01GM132432-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Neil K. Garg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,995
- **Award type:** 3
- **Project period:** 2019-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135289

## Citation

> US National Institutes of Health, RePORTER application 10135289, Harnessing Strained Intermediates to Access Complex Molecules (3R01GM132432-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135289. Licensed CC0.

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