# New Methods and Strategies for the Concise Synthesis of Complex Indole Alkaloids

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $306,814

## Abstract

PROJECT SUMMARY, ABSTRACT
The objective of this program is to develop broadly effective chemistry for the stereocontrolled chemical
synthesis of complex structures of use to chemists and medicinal chemists. The research plan is divided into
two Specific Aims, each opening access to distinct classes of natural products. Aim 1 describes the
development of an unexplored, dearomative-Claisen rearrangement, which allows functionalization of the C2
position of indoles, thereby enabling the stereocontrolled, asymmetric synthesis of 2,2-disubstituted indoline
derivatives. This new Claisen rearrangement transform will be incorporated into the design of efficient
strategies to indoline-containing natural products. Aim 2 presents the development of two [4+3]-cycloaddition
based routes for the synthesis of indole-fused cycloheptanes and the application of this chemistry to the
synthesis of the intricate and bioactive ambiguine natural products. The research plan is supported throughout
with compelling preliminary results, and the synthesis applications are designed to make maximal use of the
methodology, while addressing unmet synthetic challenges posed by the complex targets. The new chemistry
is expected to be broadly useful to organic and pharmaceutical chemists involved in drug development,
chemical synthesis, and natural product research. The final products of the total synthesis efforts and many
advanced intermediates will be submitted to a screening facility for biological testing. The proposed projects
will provide excellent training to graduate students and postdoctoral associates in chemical synthesis and
problem solving, preparing them for successful careers in the pharmaceutical industry and academia.

## Key facts

- **NIH application ID:** 10695092
- **Project number:** 5R01GM144663-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** VIRESH H. RAWAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $306,814
- **Award type:** 5
- **Project period:** 2021-09-10 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10695092

## Citation

> US National Institutes of Health, RePORTER application 10695092, New Methods and Strategies for the Concise Synthesis of Complex Indole Alkaloids (5R01GM144663-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10695092. Licensed CC0.

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