Wednesday, July 2, 2025 7/2/2025

New Methods for the Synthesis of Biologically Active Compounds

Award Number: R35GM148203
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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New Methods for the Synthesis of Biologically Active Compounds - Project Summary Our long-term goal is to develop new chemical reactions for the synthesis of compounds that could be used as medicines. We will build upon our expertise in the synthesis of cyclic peroxides, a family of natural products that exhibit a broad range of biological activities, suggesting their application to the treatment of malaria, cancer, and viral and bacterial infections. During the proposed funding period, we will investigate our hypothesis that initiation of ferroptosis is a general property of cyclic peroxides, and we will optimize the potency and metabolic stability of FINO2, a cyclic peroxide we developed that initiates cell death by a new mechanism. The target of FINO2 is unknown so we will study the mechanism by which cyclic peroxides like FINO2 initiate programmed cell death, in collaboration with Professor Brent Stockwell (Columbia University). We will also develop new methods for the synthesis of the cyclic peroxide structural motif found in many naturally occurring peroxides. We will also investigate the synthesis of aromatic peroxides, a structural class whose synthesis and reactivity have not been addressed. In the proposed funding period, we will also extend our investigations of mechanisms of acetal substitution reactions, which are important methods in natural product synthesis and carbohydrate chemistry. Using systematic studies of model systems, we can identify the factors that contribute to the stability and reactivity of oxocarbenium ions, which are intermediates involved in many of the reactions of carbohydrates, including enzymatic reactions. We will determine how the carboxyl group in sugars such as sialic acids influence the stereoselectivity of reactions involving these sugars. We will demonstrate remote neighboring-group participation as a means of controlling stereoselectivity in cyclic and acyclic compounds. The proposed research is innovative because it addresses structural types and reactive intermediates that have received little attention in the literature. The proposed research is significant because it will lead to new pathways for making biologically active compounds and will provide deeper mechanistic understanding of chemical and biological processes. These studies are relevant to human health because they could result in drugs that kill cells by unique pathways, leading to new treatments for various diseases. Furthermore, the mechanistic understanding of intermediates involved in reactions of carbohydrates could lead to new ways of designing enzyme inhibitors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $402,500 )
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	3	6/9/2025	NON-COMPETING CONTINUATION	$402,500
2025	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	2	11/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $402,500

Issue Date FY: 2024 ( Subtotal = $537,356 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	003	2	9/5/2024	SUPPLEMENT FOR EXPANSION	$64,922
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	002	2	7/29/2024	NON-COMPETING CONTINUATION	$40,250
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	2	7/2/2024	SUPPLEMENT FOR EXPANSION	$69,934
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	2	3/8/2024	NON-COMPETING CONTINUATION	$362,250
														Subtotal = $537,356

Issue Date FY: 2023 ( Subtotal = $456,863 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	1	5/26/2023	NEW	$456,863
														Subtotal = $456,863

Grand Total All Awards = $1,396,719

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New Methods for the Synthesis of Biologically Active Compounds

Award Number: R35GM148203

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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