# Synthesis and Study of Cyclotryptamine and Diketopiperazine Alkaloids

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $455,435

## Abstract

Project Summary/Abstract
The detailed study of the chemistry and biology of complex natural products at a fundamental
level provides critical insight to 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 total chemical syntheses of structurally complex
and biologically active natural products through the systematic discovery, development, and
application of new synthetic strategies and methodologies. The targets are selected based on
novelty of molecular architecture, paucity of prior synthetic studies, abundance of opportunities
for development of new strategies and methodologies, possession of significant biological
activity, and the potential for future chemical and biological studies. This program will focus on
synthetic studies of the rich family of cyclotryptamine and diketopiperazine alkaloids. Of central
interest is the directed, regioselective, stereoselective, and efficient union of cyclotryptamine
substructures 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 application of new highly selective transformations
for the rapid generation of molecular complexity. These include stereoretentive
diketopiperazine hydroxylation followed by stereocontrolled sulfidation, employing a variety of
new reagents and conditions developed in this program, to access the corresponding
epipolythiodiketopiperazines. With this program's access to potently bioactive families of
complex alkaloids and derivatives, we look for opportunities for extensive comparative analysis
of groups of compounds to gain valuable insight concerning structure-activity relationships that
can inform synthesis of designed derivatives to facilitate further biochemical collaborative
investigations. This program will continue to provide synthetic samples of rare and precious
compounds for structure validation and detailed examination of their chemistry and biology.
The well recognized biological activity of this rich family of alkaloids ensure that the many
related intermediates and derivatives accessed through these efforts will also behold great
promise both as mechanistic tools and as new bioactive compounds, and thus they will be
subject to continuous evaluation through our multidisciplinary and collaborative engagements.

## Key facts

- **NIH application ID:** 9828564
- **Project number:** 5R01GM089732-10
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mohammad Movassaghi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $455,435
- **Award type:** 5
- **Project period:** 2010-01-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828564

## Citation

> US National Institutes of Health, RePORTER application 9828564, Synthesis and Study of Cyclotryptamine and Diketopiperazine Alkaloids (5R01GM089732-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828564. Licensed CC0.

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