2453221
Project Grant
Overview
Grant Description
Computation-driven synthesis of Paxilline-type indole diterpenoids - with the support of the Chemical Synthesis (SYN) program in the Division of Chemistry.
Professor Timothy Newhouse of Yale University is studying the development of synthetic routes to diterpenoids.
The synthesis of small molecules is one of the rate-limiting steps across disciplines from materials science to medicinal chemistry.
To overcome this bottleneck in the discovery process, we need methodological advancements and improvements to the synthesis design process.
The long-term goal of this proposal is to apply computational strategies to synthetic planning to access structurally complex natural products, and in this proposal these efforts are focused on synthesis of diterpenoids.
The approach to model development described in this proposal can be applied to any synthetic transformation and would be enabling and thus broadly impactful whenever that transformation’s short-term experimental evaluation is not possible.
Moreover, strategic partnerships within and around the Yale community will bring science to K-12 audiences.
The design of a synthetic pathway to a desired molecule is generally conducted by human analysis although computational approaches are beginning to emerge.
This proposal outlines the development of several artificial intelligence-based tools to predict the yield of common carbon-carbon bond forming cyclization reactions.
Additionally, generative modelling is proposed to design ligands, substrates, and routes to natural products.
These computational methods will enable the planning and synthesis of natural products and analogs.
High-risk yet high-reward plans are de-risked through the use of machine learning models, thereby allowing efficient and expedient laboratory access to synthetically challenging molecular scaffolds.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
Subawards are not planned for this award.
Professor Timothy Newhouse of Yale University is studying the development of synthetic routes to diterpenoids.
The synthesis of small molecules is one of the rate-limiting steps across disciplines from materials science to medicinal chemistry.
To overcome this bottleneck in the discovery process, we need methodological advancements and improvements to the synthesis design process.
The long-term goal of this proposal is to apply computational strategies to synthetic planning to access structurally complex natural products, and in this proposal these efforts are focused on synthesis of diterpenoids.
The approach to model development described in this proposal can be applied to any synthetic transformation and would be enabling and thus broadly impactful whenever that transformation’s short-term experimental evaluation is not possible.
Moreover, strategic partnerships within and around the Yale community will bring science to K-12 audiences.
The design of a synthetic pathway to a desired molecule is generally conducted by human analysis although computational approaches are beginning to emerge.
This proposal outlines the development of several artificial intelligence-based tools to predict the yield of common carbon-carbon bond forming cyclization reactions.
Additionally, generative modelling is proposed to design ligands, substrates, and routes to natural products.
These computational methods will enable the planning and synthesis of natural products and analogs.
High-risk yet high-reward plans are de-risked through the use of machine learning models, thereby allowing efficient and expedient laboratory access to synthetically challenging molecular scaffolds.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
Subawards are not planned for this award.
Awardee
Funding Goals
THE GOAL OF THIS FUNDING OPPORTUNITY, "DIVISION OF CHEMISTRY: DISCIPLINARY RESEARCH PROGRAMS", IS IDENTIFIED IN THE LINK: HTTPS://WWW.NSF.GOV/PUBLICATIONS/PUB_SUMM.JSP?ODS_KEY=NSF22605
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
New Haven,
Connecticut
06511-3572
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 210% from $193,830 to $600,000.
Yale Univ was awarded
Project Grant 2453221
worth $600,000
from the Division of Chemistry in June 2025 with work to be completed primarily in New Haven Connecticut United States.
The grant
has a duration of 3 years and
was awarded through assistance program 47.049 Mathematical and Physical Sciences.
The Project Grant was awarded through grant opportunity Division of Chemistry: Disciplinary Research Programs.
Status
(Ongoing)
Last Modified 4/17/25
Period of Performance
6/1/25
Start Date
5/31/28
End Date
Funding Split
$600.0K
Federal Obligation
$0.0
Non-Federal Obligation
$600.0K
Total Obligated
Activity Timeline
Transaction History
Modifications to 2453221
Additional Detail
Award ID FAIN
2453221
SAI Number
None
Award ID URI
SAI EXEMPT
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
490309 DIVISION OF CHEMISTRY
Funding Office
490309 DIVISION OF CHEMISTRY
Awardee UEI
FL6GV84CKN57
Awardee CAGE
4B992
Performance District
CT-03
Senators
Richard Blumenthal
Christopher Murphy
Christopher Murphy
Modified: 4/17/25