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. 2016 Dec;2016(35):5799-5802.
doi: 10.1002/ejoc.201601195. Epub 2016 Nov 15.

Divergent Synthesis of Quinolone Natural Products from Pseudonocardia sp. CL38489

Stephen M Geddis  1 , Laura Carro  1 , James T Hodgkinson  1 , David R Spring  1
Affiliations

Divergent Synthesis of Quinolone Natural Products from Pseudonocardia sp. CL38489

Stephen M Geddis et al. European J Org Chem. 2016 Dec.

Abstract

Two divergent synthetic routes are reported offering access to four quinolone natural products from Pseudonocardia sp. CL38489. Key steps to the natural products involved a regioselective epoxidation, an intramolecular Buchwald-Hartwig amination and a final acid-catalysed 1,3-allylic-alcohol rearrangement to give two of the natural products in one step. This study completes the synthesis of all eight antibacterial quinolone natural products reported in the family. In addition, this modular strategy enables an improved synthesis towards two natural products previously reported.

Keywords: Antibacterial agents; Cross‐coupling; Michael addition; Natural products; Quinolones.

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Figures

Figure 1
Figure 1
Eight quinolone natural products isolated from Pseudonocardia sp. CL38489.
Scheme 1
Scheme 1
Previously employed sp2–sp3 Suzuki–Miyaura coupling to give natural products 1–4.12
Scheme 2
Scheme 2
(A) Anticipated equilibration between 5 and 6 could enable access to both products from one synthetic scheme; retrosynthesis of natural product 5. X = halogen, PG = protecting group. (B) Retrosynthesis of natural‐product quinolones 8, 4 and 7 from key natural product 1.
Scheme 3
Scheme 3
Synthesis of protected propargylic alcohol coupling partners 12 and 13 (DMAP = 4‐dimethylaminopyridine; DIPEA = N,N‐diisopropylethylamine).
Scheme 4
Scheme 4
Synthesis of natural products 5 and 6. Attempted deprotection of 16 also resulted in a partial 1,3‐allylic‐alcohol rearrangement, which allowed both to be isolated (PPTS = pyridinium p‐toluenesulfonate).
Scheme 5
Scheme 5
Synthesis of natural products 4 and 8 directly from 1 (mCPBA = meta‐chloroperoxybenzoic acid).
Scheme 6
Scheme 6
Low‐yielding conversion of 1 to 7.
Scheme 7
Scheme 7
Proposed competing dimerisation accounting for low conversion of 1 to 7.
See this image and copyright information in PMC

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