# Synthesis of Bioactive Bis-Tetrahydroisoquinoline Alkaloids

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $296,810

## Abstract

Project Summary/Abstract:
The objective of this research program is to discover and develop new reaction methods
en route to the synthesis of complex bioactive molecules. Research in our group at
Caltech is focused on the general area of chemical synthesis. Specifically, our science
has been devoted to the development of new strategies for the preparation of complex
molecules that possess significant structural, biological, and physical properties.
Concurrent with this program of target-driven synthesis is a dedicated effort directed
toward the development of new reaction methods that we anticipate will be useful for a
range of applications across numerous disciplines, including synthetic and
organometallic chemistry, chemical biology, and human medicine.
In this proposal, we outline a multifaceted and integrated program in organic synthesis
that encompasses the total synthesis of the highly biologically active natural product
jorumycin. Jorumycin, isolated from the sea slug Jorunna funebris, has been shown to
possess exceedingly potent antitumor and antibiotic activity (Gram-positive and Gram-
negative). The proposed research will provide access to jorumycin and previously
unavailable analogs to be used in further biological evaluation. We illustrate a rapid and
unusual approach to the construction a pentacyclic core, common to the members of the
bis-tetrahydroisoquinoline class of natural product. Upon completion of our target and a
host of designed analogs, we will collaborate with Dr. Dennis Slamon of the
Translational Oncology Research Laboratory at UCLA who will undertake biological
evaluation of our materials. Studies performed at UCLA in conjunction with DMPK
studies at WuXi AppTec will then indicate how we can improve upon the architectures
already developed by nature to produce efficacious small organic molecules for use as
potential chemotherapeutic agents.

## Key facts

- **NIH application ID:** 9878676
- **Project number:** 5R01GM127972-03
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** BRIAN M STOLTZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $296,810
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878676

## Citation

> US National Institutes of Health, RePORTER application 9878676, Synthesis of Bioactive Bis-Tetrahydroisoquinoline Alkaloids (5R01GM127972-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878676. Licensed CC0.

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