# Catalytic and Stereoselective C-C-Heteroatom Bond Forming Reactions

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2024 · $483,000

## Abstract

Strategies to access desirable analogues of natural products and pharmaceuticals in efficient,
practical, cost-effective, and stereoselective manners are central to organic synthesis and drug
discovery. Total synthesis of such analogues is often lengthy and inefficient, thus increasing the
time required to secure the desired molecules, as well as the cost of preparing compounds that
are important to human healthcare. Particularly attractive but challenging are schemes that
enable direct transformation of ubiquitous but otherwise chemically inert C–H bonds that are
contained in the polyfunctional bioactive molecules. We will develop catalytic processes that
entail oxidation of amine, ether, or thioether-based small molecule drugs into the corresponding
enamine, enol ether or thioenol ether derivatives; such intermediates will then be coupled with
various chemical tagging agents to generate – in a single operation – a library of drug
derivatives. The resulting compounds will contain ‘clickable’ handles that can be used as a
handle for bioconjugation. Some will carry tags for structure-activity relationship studies (e.g.,
biotin, fluorophore), and/or photoaffinity labels for chemoproteomics (e.g., arylazide, diazirine).
Various desirable analogues of N, O, and/or S-based medicinal agents will thus become readily
accessible; preparation of these entities by total synthesis would either be impossible or
substantially more cumbersome. A combination of Lewis acid and Brønsted base catalysts will
be used to promote the proposed transformations. We will utilize the above strategies to design
pathways that are significantly more efficient and broadly applicable than those previously
disclosed. Among the medicinally relevant molecules that will be subjected to the late-stage
functionalization are important anticancer agents such as alectinib, carfilzomib, and venetoclax.

## Key facts

- **NIH application ID:** 10873720
- **Project number:** 5R35GM128695-07
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Masayuki Wasa
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,000
- **Award type:** 5
- **Project period:** 2018-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873720

## Citation

> US National Institutes of Health, RePORTER application 10873720, Catalytic and Stereoselective C-C-Heteroatom Bond Forming Reactions (5R35GM128695-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873720. Licensed CC0.

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