Synthesis of the C1-C27 Fragment of Stambomycin D Validates Modular Polyketide Synthase-Based Stereochemical Assignments.

Jieyan Lim,Haraldur G Gudmundsson,Venkaiah Chintalapudi,Lijiang Song,Alice Bernasconi,Gregory L Challis,Minh Tran,Edward A Anderson,Araceli Blanco

doi:10.1021/acs.orglett.1c02650

Abstract

The stambomycins are a family of bioactive macrolides isolated from Streptomyces ambofaciens. Aside from two stereocenters installed through cytochrome P450 oxidations, their stereochemistry has been predicted by sequence analysis of the polyketide synthase. We report a synthesis of the C1–C27 fragment of stambomycin D, the spectroscopic data of which correlates well with that of the natural product, further validating predictive sequence analysis as a powerful tool for stereochemical assignment of complex polyketide natural products.

Highlights

The stambomycins are a family of bioactive macrolides isolated from Streptomyces ambofaciens
Stereochemical determination is a key element in natural product discovery, as bioactivity is often intrinsically linked to stereochemistry
Letter stambomycins are one of the earliest structurally complex polyketides for which predictive sequence analysis was employed for stereochemical assignment, and remain one of the most elaborate examples to date.[16]

Summary

Corresponding Author

Anderson − Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K.; orcid.org/ 0000-0002-4149-0494; Email: edward.anderson@ chem.ox.ac.uk. Jieyan Lim − Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K. Venkaiah Chintalapudi − Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K. Haraldur G. Gudmundsson − Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K. Minh Tran − Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, U.K. Alice Bernasconi − Sezione Chimica Generale e Organica “A. Lijiang Song − Department of Chemistry and Warwick Integrative Synthetic Biology Centre, University of Warwick, Coventry CV4 7AL, U.K. Gregory L. Challis − Department of Chemistry and Warwick Integrative Synthetic Biology Centre, University of Warwick, Coventry CV4 7AL, U.K.; Department of Biochemistry and Molecular Biology and ARC Centre of Excellence for Innovations in Peptide and Protein Science, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; orcid.org/0000-0001-5976-3545.

■ ACKNOWLEDGMENTS

Findings

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