# Extended aromatic polyheterocycles via scaffold-guided photoinduced cascades

> **NIH NIH R15** · UNIVERSITY OF DENVER (COLORADO SEMINARY) · 2020 · $434,710

## Abstract

It took half a century for the CAS database to clear a symbolic milestone of 100M compounds
in 2015. Only four years later, this number stands at 156M, attesting to an impressive growth of
productivity in a large part driven by drug design and discovery. Yet, the rate of FDA approvals
of new molecular entities, excluding the biologics, has been anemic for a long time, oscillating
between 10 and 30 annually. Such a small yield was explained, in part, by the lack of truly new
and complex structures in the pipeline, which in turn, could be because a very limited number of
synthetic reactions happen to dominate the chemical landscape of modern medicinal chemistry.
This makes new methods development critically important for synthetic chemistry.
 Given the recent rise of synthetic photochemistry, which is becoming a broadly accepted tool
in the toolbox of organic and medicinal chemistry, our overall goal is to discover new
photoinduced reactions and develop them into robust and powerful synthetic methodologies. In
this proposal, we will focus our effort on three unprecedented reactions offering rapid access to
aromatic polyheterocyclic molecular architectures via (i) a new photoinduced cascade initiated
by the excited state proton transfer (ESIPT) with post-photochemical decarboxylative
aromatization of the primary photoproducts, (ii) a new photoinduced cascade involving a 6e-
electrocyclization in aromatic imines followed by a photoinduced formation of a nitrene and
subsequent electrocyclization or rearrangement, and finally (iii) a new hydrogen atom transfer
(HAT)-initiated photoinduced cascade leading to complex fused pyrroloquinazolinones. In the
context of diversity-oriented synthesis of complex aromatic polyheterocycles, this proposal
outlines a clear path to new molecular architectures occupying an unexplored or underexplored
areas of chemical space. The broad objective is to generate potential pharmacophores by
systematically sampling the chemical space with diversified core structures augmented with a
range of peripheral functionalities.
 Adding three new powerful photoinduced cascades to the arsenal of synthetic chemistry is
innovative and impactful. With several indications of biological activity in the preliminary studies,
this project will involve targeted biological screening of compounds synthesized in the course of
this study. Also, as an AREA R15, this multifaceted project will provide ample training
opportunities for undergraduate research students in the PI’s lab. The students will be involved
with synthesis, learn photochemistry and photophysics, molecular modeling, spectra analysis
and prediction, and gain initial understanding of medicinal chemistry and biological screening.

## Key facts

- **NIH application ID:** 10046898
- **Project number:** 1R15GM139145-01
- **Recipient organization:** UNIVERSITY OF DENVER (COLORADO SEMINARY)
- **Principal Investigator:** ANDREI G KUTATELADZE
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,710
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046898

## Citation

> US National Institutes of Health, RePORTER application 10046898, Extended aromatic polyheterocycles via scaffold-guided photoinduced cascades (1R15GM139145-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046898. Licensed CC0.

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