Approaches to the Syntheses of the Acyltetramic Acid Antibiotics Streptolydigin, Tirandamycin A, and Tirandamycin B

Citation

Smith, Michael Glenn (1986) Approaches to the Syntheses of the Acyltetramic Acid Antibiotics Streptolydigin, Tirandamycin A, and Tirandamycin B. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/w9jw-bw56. https://resolver.caltech.edu/CaltechTHESIS:03012019-123946315

Abstract

An approach to the syntheses of several acyltetramic acid antibiotics is presented. The approach is partially based on a previous synthesis of tirandamycic acid. It involves an ester enolate Claisen rearrangement of an intermediate derived from D-glucose to establish the requisite relative and absolute stereochemical configurations. An application of the Sharpless asymmetric epoxidation reaction is also involved, and is noteworthy due to its success as an intramolecular kinetic resolution of two available allylic alcohols.

A total synthesis of streptolic acid is presented as evidence of the viability of the synthetic scheme employed. A formal synthesis of tirandamycin A is also presented. Furthermore, the sequence employed is shown to provide an excellent approach to tirandamycin B.

A novel de-benzylation is also reported. The reagent lithium di-tert-butylbiphenyl is demonstrated to accomplish the deprotection of benzyl ethers rapidly and efficiently.

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