Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2012; 44(23): 3688-3692
DOI: 10.1055/s-0032-1317490
DOI: 10.1055/s-0032-1317490
paper
Synthesis of Both Enantiomers of the Streptomyces Alkaloid 4-epi-SS20846A
Further Information
Publication History
Received: 03 August 2012
Accepted after revision: 27 September 2012
Publication Date:
24 October 2012 (online)
Abstract
The enantiodivergent synthesis of the Streptomyces alkaloid 4-epi-SS20846A was based on a Takai olefination/Suzuki–Miyaura coupling sequence for the highly stereoselective introduction of the E,E-pentadienyl side chain on the piperidine skeleton. Optical separation of a key hydroxylated enamide ester, prepared by palladium-catalyzed methoxycarbonylation of a lactam-derived enol phosphate, was successfully achieved by both lipase-catalyzed kinetic resolution and semipreparative HPLC. This approach allowed us to obtain the enantiopure target alkaloid in 35–38% yield over six steps.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
- Supporting Information
-
References
- 1 Grabley S, Hammann P, Kluge H, Wink J, Kricke P, Zeeck A. J. Antibiot. 1991; 44: 797
- 2 Komoto T, Yano K, Ono J, Okawa J, Nakajima T. JP Kokai 35788, Feb 20, 1986 ; Chem. Abstr. 1986, 105, 132137w.
- 3a Takemoto Y, Ueda S, Takeuchi J, Nakamoto T, Iwata C. Tetrahedron Lett. 1994; 35: 8821
- 3b Takemoto Y, Ueda S, Takeuchi J, Baba Y, Iwata C. Chem. Pharm. Bull. 1997; 45: 1906
- 3c Yokohama H, Otaya K, Yamaguchi S, Hirai Y. Tetrahedron Lett. 1998; 39: 5971
- 3d Davis FA, Chao B, Fang T, Szewczyk JM. Org. Lett. 2000; 2: 1041
- 3e Sabat M, Johnson CR. Tetrahedron Lett. 2001; 42: 1209
- 4a Ripoche I, Canet J.-L, Aboab B, Gelas J, Troin Y. J. Chem. Soc., Perkin Trans. 1 1988; 3485
- 4b Celestini P, Danieli B, Lesma G, Sacchetti A, Silvani A, Passarella D, Virdis A. Org. Lett. 2002; 4: 1367
- 5a Occhiato EG, Scarpi D, Guarna A, Tabasso S, Deagostino A, Prandi C. Synthesis 2009; 3611
- 5b Bartali L, Casini A, Guarna A, Occhiato EG, Scarpi D. Eur. J. Org. Chem. 2010; 5831
- 5c Optical rotation values for (R)-13: [α]D 24 +127.1 (c 0.64, CHCl3); for (2S,4R)-14: [α]D 23 –11.9 (c 0.45, CHCl3).
- 6 Vink MK. S, Schortinghuis CA, Luten J, van Maarseveen JH, Schoemaker HE, Hiemstra H, Rutjes FP. J. T. J. Org. Chem. 2002; 67: 7869
- 7 The preparation of the lactam-derived enol phosphate and subsequent palladium-catalyzed methoxycarbonylation were carried out as reported in ref. 5b, but the latter at 75 °C and with 80 equivalents of MeOH.
- 8 Occhiato EG, Scarpi D, Guarna A. Eur. J. Org. Chem. 2008; 524
- 9 The formation of the unwanted compound 11 is easily revealed by the multiplets at 5.99–5.93 ppm (1 H) and 5.66–5.58 ppm (2 H) assignable to the olefinic protons of 11 in the 1H NMR spectrum of the mixture.
- 10 Occhiato EG, Casini A, Guarna A, Scarpi D. Eur. J. Org. Chem. 2011; 6544
- 11 As an alternative to the scalable kinetic resolution, it is possible to also carry out the enantiomeric separation by semipreparative HPLC, which allows 1 mmol of each enantiomer, with ee higher than 99.9%, to be obtained: Chiralpack IC semipreparative column (10 × 250 mm, 5 μm, Daicel, Osaka, Japan), isocratic elution with heptane–EtOH (7:3), flow 4.7 mL/min. Analytical: Chiralpak IC column (4.6 × 250 mm, 5 μm) at 1 mL/min. Retention times: (R)-4 (7.69 min), (S)-4 (12.74 min).
- 12 Chackalamannil S, Davies RJ, Wang Y, Asberom T, Doller D, Wong J, Leone D, McPhail AT. J. Org. Chem. 1999; 64: 1932
- 13 Takai K, Nitta K, Utimoto K. J. Am. Chem. Soc. 1986; 108: 7408
- 14 Gillis EP, Burke MD. Aldrichimica Acta 2009; 42: 17
- 15 Lee SJ, Anderson TM, Burke MD. Angew. Chem. Int. Ed. 2010; 49: 8860
- 16 Knapp DM, Gillis EP, Burke MD. J. Am. Chem. Soc. 2009; 131: 6961
- 17 Aldrich 701831. In the 1H NMR (CDCl3) spectrum of the commercial compound, the cis-isomer has diagnostic signals at 6.37 (m) and 5.26 (dq) ppm.
- 18 In compound 18, as well as in compounds 14–17, the two piperidine ring substituents are axially oriented, as shown by the low coupling constant values for the equatorial protons at C2 and C4 (highest is 6.6 Hz for 2-H in the aldehyde) as well as the lack of NOE effect between 2-H and 4-H with axial 6-H. This is due to the presence of the N-protection which forces the substituent at C2 into an axial orientation to remove the A(1,3) strain with it; see: Comins DL, Joseph SP. In Advances in Nitrogen Heterocycles . Vol. 2. Moody CJ. JAI Press; Greenwich, CT: 1996: 251-294