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. 2017 Sep 25;8(1):679.
doi: 10.1038/s41467-017-00787-y.

Stereoselective one-pot synthesis of polypropionates

Guo-Ming Ho  1 , Medel Manuel L Zulueta  1 , Shang-Cheng Hung  2
Affiliations

Stereoselective one-pot synthesis of polypropionates

Guo-Ming Ho et al. Nat Commun. .

Abstract

Polypropionates-motifs with alternating methyl and hydroxy groups-are important segments of many natural products possessing high bioactivity and therapeutic value. Synthetic access to these structures remains an area of intensive interest, focusing on the establishment of the contiguous stereocentres and a desire for operational simplicity. Here we report an efficient strategy for the stereoselective assembly of polypropionates with three or four stereocentres through a three-step relay process that include Diels-Alder reaction, silylenol ether hydrolysis and Baeyer-Villiger oxidation. The stereochemistry and functionality of the resulting polypropionates depend on the substitution pattern of the diene and dienophile substrates of the Diels-Alder cycloaddition. More importantly, the relay sequence is effectively performed in one pot, and the product could potentially undergo the same sequence for further elaboration. Finally, the C1-C9 segment of the macrolide etnangien is constructed with four of the six stereogenic centres established using the relay sequence.Polypropionates are present in many natural products possessing high bioactivity and therapeutic value. Here the authors show a strategy for the stereoselective assembly of polypropionates with three or four stereocentres through a process that includes a Diels-Alder reaction, silylenol ether hydrolysis and Baeyer-Villiger oxidation.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Polypropionate-containing natural products. The major polypropionate segments are marked by dashed polygons
Fig. 2
Fig. 2
Our retrosynthetic analysis for the synthesis of polypropionates. The asterisks represent possible stereogenic centres. TBS tert-butyldimethylsilyl
Fig. 3
Fig. 3
Stepwise preparation of polypropionate 14. a Synthetic route. b X-ray crystal structure of 11. DBU 1,8-diazabicyclo[5.4.0]undec-7-ene; LiHMDS lithium hexamethyldisilazide; mCPBA, meta-chloroperoxybenzoic acid; TBAF, tetrabutylammonium fluoride; Tf, triflyl; TFA, trifluoroacetic acid; THF, tetrahydrofuran
Fig. 4
Fig. 4
Synthesis of the C1–C9 fragment of etnangien. a Synthetic route. b X-ray crystal structure of 41. c X-ray crystal structure of 42. Ac, acetyl, DMAP, N,N-dimethyl-4-aminopyridine; PCC, pyridinium chlorochromate
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