# Development of New Strategies for Chemical Synthesis and Study of Complex Natural Products

> **NIH NIH R35** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $737,381

## Abstract

Project Summary/Abstract
The detailed study of the fundamental chemistry and biological properties of complex natural
products provides critical insight toward understanding their mode of action and enables
development of new approaches for treatment of various human ailments. This research
program focuses on the development of efficient and concise strategies for the total chemical
syntheses of structurally complex and biologically active natural products. The target
compounds are selected based on novelty of molecular architecture and associated
challenges, paucity of prior synthetic studies, abundance of opportunities for development of
new synthetic strategies and methodologies, possession of significant biological activity, and
the potential for future chemical and biological studies. The systematic discovery,
development, and application of new synthetic strategies and methodologies explored in this
program continue to provide synthetic samples of rare and precious compounds for structure
validation and detailed examination of their chemistry and biology. This program focuses on
synthetic studies of the rich families of complex natural products including cyclotryptamine,
diketopiperazine, and monoterpene indole alkaloids. A central interest is the development of
generalizable directed, regioselective, stereoselective, and efficient union of complex
fragments providing late-stage couplings to secure challenging linkages, including complete
stereocontrol at quaternary stereogenic centers. Convergent and guided assembly of
advanced fragments is complemented by development and application of new highly selective
chemical transformations for the rapid generation of molecular complexity. These
transformations include new methods for amide derivatization, azaheterocycle syntheses,
cascade bond–forming reactions involving enamines, stereoretentive hydroxylation of complex
substrates, and stereocontrolled sulfidation made possible through employing new reagents
and conditions developed in this program. This program’s access to potently bioactive
collection of families of complex alkaloids and related derivatives continues to enables exciting
biochemical collaborative investigations. The array of synthetic molecules accessed through
this program behold great promise as new bioactive compounds and mechanistic tools, and
these compounds are continually evaluated and examined through multidisciplinary
collaborations.

## Key facts

- **NIH application ID:** 10390371
- **Project number:** 5R35GM141963-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mohammad Movassaghi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $737,381
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390371

## Citation

> US National Institutes of Health, RePORTER application 10390371, Development of New Strategies for Chemical Synthesis and Study of Complex Natural Products (5R35GM141963-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10390371. Licensed CC0.

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