# SYNTHESIS OF MACROLIDE ANTIBIOTICS

> **NIH NIH R01** · OREGON STATE UNIVERSITY · 1987 · $192,245

## Abstract

The objective of this research is to devise and develop novel and efficient
pathways for the total synthesis of certain macrolide antibiotics.  The
strategy to be employed involves stereocontrolled elaboration of specific
subunits of these structures in optically pure form, followed by linkage of
these segments in a convergence upon the target molecule.

Exemplifying this approach, the broad spectrum anthelmintic agent,
avermectin B1a is to be constructed from segments representing the
hexahydrobenzofuranone nucleus, the spiro ketal moiety, and a linear insert
between these units.  Final closure of the macrolide is envisioned by
translactonization employing a Beta-lactone.  The dimeric macrolide
ionophores boromycin and aplasmomycin will be assembled from their half
structures which have already been completed.  Improved methods are
proposed for synthesis of the pyran and tetrahydrofuran components of these
structures and for installation of the glycollate at the terminus of the
half structures.  New variations are set forth for the synthesis of
verrucarol, the trichothecanoid nucleus of the cytotoxic antibiotic
verrucarin A, and for elaboration of the related T2 toxin.  The key to
establishing the functionalized C ring of verrucarol will be an
intramolecular photochemical cycloaddition of a vinyl ester, followed by
ring expansion of a cyclobutyl carbinol.  The pyran ring of latruculin B,
and unusual cysteine-containing macrolide from a marine source and a potent
cholinesterase inhibitor, is to be synthesized by means of a hetero
Diels-Alder reaction, for which the diene component will be derived from
segments connected via Wittig reactions.  The synthesis of pseudomonic acid
C, a broad-spectrum antibacterial agent which is strongly bound to human
serum, focuses on the central tetrahydropyran nucleus.  This is to be
constructed in an entiospecific manner employing borneol as chiral
auxiliary.

## Key facts

- **NIH application ID:** 3124861
- **Project number:** 5R01AI010964-14
- **Recipient organization:** OREGON STATE UNIVERSITY
- **SAM.gov UEI:** MZ4DYXE1SL98
- **Principal Investigator:** JAMES D WHITE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $192,245
- **Award type:** 5
- **Project period:** 1979-01-01 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124861

## Citation

> US National Institutes of Health, RePORTER application 3124861, SYNTHESIS OF MACROLIDE ANTIBIOTICS (5R01AI010964-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124861. Licensed CC0.

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