Total Synthesis of a Hemiacetal Polypropionate from Siphonaria australis

Troy Lister; Michael V. Perkins

doi:10.1071/CH04039

RESEARCH ARTICLE

Previous Next Contents Vol 57(8)

Total Synthesis of a Hemiacetal Polypropionate from Siphonaria australis

Troy Lister ^A and Michael V. Perkins ^A ^B

+ Author Affiliations

- Author Affiliations

^A School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide SA 2001, Australia.

^B Author to whom correspondence should be addressed (e-mail: mike.perkins@flinders.edu.au).

Australian Journal of Chemistry 57(8) 787-797 https://doi.org/10.1071/CH04039
Submitted: 15 February 2004 Accepted: 20 April 2004 Published: 10 August 2004

Abstract

A highly stereocontrolled synthesis of (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one has been achieved in 13 steps and an overall yield of 7.6% from (R)-(+)-4-benzyloxazolidin-2-one. This substrate-controlled asymmetric synthesis utilized Paterson’s lactate-derived chiral ketone (2S)-2-(benzoyloxy) pentan-3-one to generate the 5R and 6S stereocentres and alkylation of an Evans’ auxiliary to generate the remote side-chain 3R stereocentre. Furthermore, a novel, highly efficient, and selective strategy was used to generate an enol trimethylsilyl ether whose subsequent Mukaiyama aldol condensation gave the acyclic precursor to the final product. A thermodynamically controlled cyclization then gave (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one with control of the 2S and 3R stereocentres. The NMR spectroscopic data and optical rotation obtained for synthetic (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one were consistent with those reported for the hemiacetal isolated from Siphonaria australis, and thus, prove the absolute and relative configuration of the natural product.

Acknowledgments

We thank the Australian Research Council (Flinders University Small ARC Grant to M.V.P.) for support. We also thank Ms Catherine M. Sincich, Professor William Fenical, and the late Professor D. John Faulkner, Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, for kindly providing copies of the original ¹H NMR spectra for hemiacetal 1 and ester 2 from the Hochlowski and Faulkner^[3] isolation.

References

[1] M. T. Davies-Coleman, M. J. Garson, Nat. Prod. Rep. 1998, 15, 477.

        | Crossref | GoogleScholarGoogle Scholar |

        | Crossref | GoogleScholarGoogle Scholar |

        | Crossref | GoogleScholarGoogle Scholar |
        | Crossref | GoogleScholarGoogle Scholar |
        | Crossref | GoogleScholarGoogle Scholar |
        | Crossref | GoogleScholarGoogle Scholar |
        | Crossref | GoogleScholarGoogle Scholar |




[13] The ¹H NMR spectrum was reported^[3] to be recorded in CDCl₃, but copies of the original spectra sent to us were marked CCl₄. The ¹H NMR spectrum of compound 7 recorded in CCl₄ (with external C₆D₆ lock) was identical to that reported for hemicacetal 1 in ref. [3].

[14] The ¹³C NMR (C₆D₆) spectrum reported^[3] for hemacetal 1 was identical to that found for hemiacetal 7 except for C7 (81.5 compared with 82.8 ppm). Unfortunately, original copies of the ¹³C NMR spectra could not be located for direct comparison. It is possible that the reported shifts for the C7 signals of hemiacetal 1 and ester 2 were inadvertently interchanged.

[15] Copies of the original ¹H NMR spectra of hemiacetal 1 and ester 2 in both C₆D₆ and CCl₄ were obtained for comparison.

Total Synthesis of a Hemiacetal Polypropionate from Siphonaria australis

Abstract

Acknowledgments

Subscriber Login