# SYNTHESIS OF ANTIBIOTICS

> **NIH NIH R01** · YALE UNIVERSITY · 1992 · $348,867

## Abstract

The long-term objectives of this project involve the development of new
synthetic strategies and the application of these strategies to the
synthesis of complex systems of biological interest.  In the AI program
we hope to apply these capabilities to the synthesis of substances of
interest as potential antibiotics, antiviral agents, or as antitumor
drugs.

In this next grant period we will focus on a broad range of chemical
goals with diverse biological implications.  A major and comprehensive
effort is envisioned in the synthesis of oligosaccharides.  We will study
a potential menu of reactions whereby glycals will be substrates for
electrophilically induced glycosidation.  Included in this work are 2-
deoxy, 2-halo, 2-amino, and "normal" 2-oxygenated oligosaccharides.  The
ultimate goal is the development of a capability in polymer based
oligosaccharide construction.  Specific targets in the carbohydrate area
will be novel glycosides of avermectin and adriamycin, as well as the
full carbohydrate portion of allosamidin.  A study of the use of these
concepts for the synthesis of novel nucleosides of interest in anti-AIDS
therapy will be launched.

Some new strategies in the synthesis of heterocycles have been developed.
The application of these findings to the total synthesis of several key
target systems will be pursued.  Particularly interesting in this regard
are castanospermine and FR900482.  Castanospermine has been shown to have
some anti-AIDS potential as an inhibitor of enzymes responsible for
glycoprotein  maturation.  FR900482 has engendered considerable interest
due to its very novel structure and reported "exceptionally potent"
antitumor activity.

We also will be directing a great deal of effort to the synthesis of
esperamicin.  Here the challenge goes beyond the complexity of the
synthetic problem.  Through suitable structures, which can be obtained
uniquely through synthesis, a better understanding of the mode of action
of this important antitumor agent will be achieved.

A major effort will be directed toward the total synthesis of FK-506.
This compound is the most powerful immunosuppressant now known (100 more
active than cyclosporine).  We will also continue our quinone-
hydroquinone chemistry in the context of the biomimetic chemistry of
adriamycin.  Through these studies a superior insight into the mode of
action of the antaracyclines will be sought.  The completion of our
efforts in the tunicamycin area is envisioned.  At the present time the
only remaining problem is the construction of the trehalose type of
linkage.

## Key facts

- **NIH application ID:** 3126919
- **Project number:** 5R01AI016943-13
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** SAMUEL J DANISHEFSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $348,867
- **Award type:** 5
- **Project period:** 1980-03-01 → 1994-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126919

## Citation

> US National Institutes of Health, RePORTER application 3126919, SYNTHESIS OF ANTIBIOTICS (5R01AI016943-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126919. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*