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Synlett 2019; 30(14): 1632-1642
DOI: 10.1055/s-0037-1611866
DOI: 10.1055/s-0037-1611866
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Evolution of a Chemical Strategy Toward the Synthesis of Unsymmetrically Oxidized Nuphar Alkaloids
This work was supported by the National Institutes of Health (NIH) – National Institute of General Medical Sciences (NIGMS R01, Grant No. 077379). J.J.L. was supported by a UCSB Chancellor’s Fellowship. Funding for the UCSB MRL Mass Spectrometry Facility was provided by the MRSEC Program of the National Science Foundation (NSF, under award NSF DMR 1121053).Further Information
Publication History
Received: 29 April 2019
Accepted after revision: 21 May 2019
Publication Date:
27 June 2019 (online)
Abstract
Here we describe the frustrations, joys, and unexpected turns experienced in our journey toward a successful strategy directed at the total synthesis of unsymmetrically oxidized Nuphar thioalkaloids. While many adjustments were made to our initial synthesis plan, our general approach to the construction of the central bis(spirothiolane) moiety remained unchanged. Specifically, each iteration of our synthesis design involved the formation of the thiaspirane motif through the stereodivergent coupling of a thietane with a metal carbenoid, followed by a Stevens-type rearrangement of the resulting sulfonium ylide.
1 Introduction
2 First-Generation Strategy
3 Second-Generation Strategy
4 Third-Generation Strategy
5 Conclusion
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References and Notes
- 1a Achamatowicz O, Bellen Z. Tetrahedron Lett. 1962; 3: 1121
- 1b Achamatowicz O, Wróbel JT. Tetrahedron Lett. 1964; 5: 129
- 1c Achamatowicz O, Banaszek H, Spiteller G, Wróbel JT. Tetrahedron Lett. 1964; 5: 927
- 2a LaLonde RT, Wong C. Pure Appl. Chem. 1977; 49: 169 ; and references therein
- 2b Birnbaum J. Tetrahedron Lett. 1965; 6: 4149
- 2c Okamura S, Nishiyama E, Yamazaki T, Otsuka N, Taniguchi S, Ogawa W, Hatano T, Tsuchiya T, Kuroda T. Biochim. Biohpys. Acta, Gen. Subj. 2015; 1850: 1245
- 2d Ozer J, Levi T, Golan-Goldhirsh A, Gopas J. Ethnopharmacol. 2015; 161: 86
- 2e Cullen WP, LaLonde RT, Wang CJ, Wong CF. J. Pharm. Sci. 1973; 62: 826
- 2f List B. Synlett 2001; 1675
- 2g Harb HY, Procter DJ. Synlett 2012; 23: 6
- 2h Müller TJ. J. Synthesis 2012; 44: 159
- 2i Kocienski P. Synfacts 2012; 8: 5
- 3a Matsuda H, Shimoda H, Yoshikawa M. Bioorg. Med. Chem. 2001; 9: 1031
- 3b Yamahara J, Shimoda H, Matsuda H, Yoshikawa M. Biol. Pharm. Bull. 1996; 19: 1241
- 3c Kolotilo NV, Sinitsa AA, Rassukana YV, Onys’ko PP. Zh. Obshch. Khim. 2006; 76: 1260 ; Chem. Abstr. 2006, 146, 316980
- 4a Matsuda H, Yoshida K, Miyagawa K, Nemoto Y, Asao Y, Yoshikawa M. Bioorg. Med. Chem. 2006; 16: 1567
- 4b Irgolic KJ. In Houben-Weyl, 4th ed., Vol. E12b. Klamann D. Thieme; Stuttgart: 1990: 150
- 5 Matsuda H, Morikawa T, Oda M, Asao Y, Yoshikawa M. Bioorg. Med. Chem. 2003; 13: 4445
- 6 Ozer J, Eisner N, Ostrozhenkova E, Bacher A, Eisenreich W, Benharroch D, Golan-Goldhirsh A, Gopas J. Cancer Biol. Ther. 2009; 8: 1860
- 7a Bates RW, Lim CJ. Synlett 2010; 866
- 7b Stoye A, Quandt G, Brunnhöfer B, Kapatsina E, Baron J, Fischer A, Weymann M, Kunz H. Angew. Chem. Int. Ed. 2009; 46: 2228
- 7c Davis FA, Santhanaraman M. J. Org. Chem. 2006; 71: 4222
- 7d Katoh M, Mizutani H, Honda T. Heterocycles 2006; 69: 193
- 7e Katoh M, Mizutani H, Honda T. Tetrahedron Lett. 2005; 46: 5161
- 7f Goodenough KM, Moran WJ, Raubo P, Harrity JP. A. J. Org. Chem. 2005; 70: 207
- 7g Moran WJ, Goodenough KM, Raubo P, Harrity JP. A. Org. Lett. 2003; 5: 3427
- 7h Barluenga J, Anzar F, Ribas C, Valdes C. J. Org. Chem. 1999; 64: 3736
- 7i LaLonde RT, Muhammad N, Wong CF, Sturiale ER. J. Org. Chem. 1980; 45: 3664
- 7j LaLonde RT, Muhammad N, Wong CF. J. Org. Chem. 1977; 42: 2113
- 7k Bates RW, Lim CJ, Collier SJ, Sukumaran J. Asian J. Org. Chem. 2015; 4: 652
- 8 Jansen DJ, Shenvi RA. J. Am. Chem. Soc. 2013; 135: 1209
- 9 Wong CF, LaLonde RT. Experientia 1975; 31: 15
- 10 Shenvi and co-workers also prepared a series of monomeric ene-iminium Nuphar analogues in an effort to elucidate the biological mechanism of action of the Nuphar alkaloids. See: Tada N, Jansen DJ, Mower MP, Blewett MM, Umotoy JC, Cravatt BF, Wolan DW, Shenvi RA. ACS Cent. Sci. 2016; 2: 401
- 11 Korotkov AK, Li H, Chapman CW, Xue H, MacMillan JB, Eastman A, Wu J. Angew. Chem. Int. Ed. 2015; 54: 10604
- 12a Li H, Cooke TJ, Korotkov A, Chapman CW, Eastman A, Wu J. J. Org. Chem. 2017; 82: 2648
- 12b Li H, Korotkov A, Chapman CW, Eastman A, Wu J. Angew. Chem. Int. Ed. 2016; 55: 3509
- 13 Mallick DJ, Korotkov A, Li H, Wu J, Eastman A. Cell Biol. Toxicol. 2019;
- 14a Yu K, Lu P, Jackson JJ, Nguyen TA. D, Alvarado J, Stivala CE, Ma Y, Mack KA, Hayton TW, Collum DB, Zakarian A. J. Am. Chem. Soc. 2017; 139: 527
- 14b Ma Y, Stivala CE, Wright AM, Hayton T, Liang J, Keresztes I, Lobkovsky E, Collum DB, Zakarian A. J. Am. Chem. Soc. 2013; 135: 16853
- 14c Stivala CE, Zakarian A. J. Am. Chem. Soc. 2011; 133: 11936
- 15 Lu P, Herrmann AT, Zakarian A. J. Org. Chem. 2015; 80: 7581
- 16 Nair V, Nair SM, Mathai S, Liebscher J, Ziemer B, Narsimulu K. Tetrahedron Lett. 2004; 45: 5759
- 17 The use of lactate as a chiral auxiliary was based on precedence from the Davies group: Davies HM. L, Huby NJ. S, Cantrell WR. Jr, Olive JL. J. Am. Chem. Soc. 1993; 115: 9468
- 18a Samojlowicz C, Grela K. ARKIVOC 2011; (iv): 71
- 18b Shon Y, Lee TR. Tetrahedron Lett. 1997; 38: 1283
- 19a Trost BM, O’Boyle BM, Torres W, Ameriks MK. Chem. Eur. J. 2011; 17: 7890
- 19b Luo Y, Zhang G, Hwang ES, Wilcoxon TA, Zhang L. Beilstein J. Org. Chem. 2011; 7: 596
- 19c Zhang G, Luo Y, Wang Y, Zhang L. Angew. Chem. Int. Ed. 2011; 50: 4450
- 19d Bates RW, Ng PS. Tetrahedron Lett. 2011; 52: 2969
- 19e Tshukao A, Oikawa D, Sakai K, Okamoto S. Tetrahedron Lett. 2008; 49: 6529
- 19f Zhang Z, Liu C, Kinder RE, Han X, Qian H, Widenhoefer RA. J. Am. Chem. Soc. 2006; 128: 9066
- 19g Meguro M, Yamamoto Y. Tetrahedron Lett. 1998; 39: 5421
- 19h Arseniyadis S, Gore J. Tetrahedron Lett. 1983; 24: 3997
- 20 Ohmura T, Hartwig JF. J. Am. Chem. Soc. 2002; 124: 15164
- 21 Amat M, Griera R, Fabregat R, Bosch J. Tetrahedron: Asymmetry 2008; 19: 1233
- 22a Gillingham D, Fei N. Chem. Soc. Rev. 2013; 42: 4918
- 22b Brown DS, Elliot MC, Moody CJ, Mowlem TJ, Marino JP. Jr, Padwa A. J. Org. Chem. 1994; 59: 2447
- 22c Reddy RP, Lee GH, Davies HM. L. Org. Lett. 2006; 8: 3437
- 22d Liu Y, Shao X, Zhang P, Lu L, Shen Q. Org. Lett. 2015; 17: 2752
- 22e Hari DP, Waser J. J. Am. Chem. Soc. 2016; 138: 2190
- 22f Clark JS, Whitlock G, Jiang S, Onyia N. Chem. Commun. 2003; 2578
- 22g Marmasäter FP, West FG. J. Am. Chem. Soc. 2001; 123: 5144
- 23 Nicolaou KC, Postema MH. D, Miller ND, Yang G. Angew. Chem., Int. Ed. Engl. 1997; 36: 2821
- 24a LaLonde RT, Donvito TN, Tsai AI. M. Can J. Chem. 1975; 53: 1714
- 24b LaLonde RT, Wong CF, Cullen WP. Tetrahedron Lett. 1970; 11: 4477
- 25a Tian M, Yan M, Baran PS. J. Am. Chem. Soc. 2016; 138: 14234
- 25b Bajtos B, Yu M, Zhao H, Pagenkopf BL. J. Am. Chem. Soc. 2007; 129: 9631
- 25c Lee YS, Cho DJ, Kim SN, Choi JH, Park H. J. Org. Chem. 1999; 64: 9727
- 26 O’Leary DJ, Blackwell HE, Washenfelder RA, Miura K, Grubbs RH. Tetrahedron Lett. 1999; 40: 1091
- 27 Dong Q, Anderson E, Ciufolini MA. Tetrahedron Lett. 1995; 36: 5681
- 28 The fixed axial orientation of the nitrogen lone pair is confirmed by the presence of Bohlman bands in the IR spectra of Nuphar alkaloids; see ref. 2a.
- 29a Ref. 24.
- 29b Yoshikawa M, Murakami T, Wakao S, Ishikado A, Murakami N, Yamahara J, Matsuda H. Heterocycles 1997; 45: 1815
- 29c LaLonde RT, Wong CF, Das KC. J. Org. Chem. 1974; 39: 2892
- 29d Martin TI, MacLean DB, Wróbel JT, Iwanow A, Starzec W. Can. J. Chem. 1974; 52: 2705
- 29e LaLonde RT, Wong CF, Das KC. J. Am. Chem. Soc. 1973; 95: 6342
- 30 Lacharity JJ, Fournier J, Lu P, Mailyan AK, Herrmann AT, Zakarian A. J. Am. Chem. Soc. 2017; 139: 13272
Initial isolation of monomeric Nuphar alkaloids was first reported in 1962:
The isolation of the dimeric alkaloids was reported later in 1964, see:
For structural characterization studies on the nuphar alkaloids, see
For explorations into the antibiotic and anti-inflammatory activity of the Nuphar alkaloids, see:
For additional synthetic studies on monomeric Nuphar alkaloids after 2013, see:
Sulfur has been shown to poison RCM reactions in other examples, see:
For selected examples of metal-catalyzed allene aminations to form vinyl piperidines, see:
For a review on the formation of rhodium and copper carbenoids, see:
For selected examples of the use of the catalysts see in Scheme [9] in metal-carbenoid chemistry, see:
The thiaspirane stereochemistry of compounds 59a, C7-epi-59a, C7-epi-59b and the corresponding deallyloxycarbonylated compounds 60a, C7-epi-60a, and C7-epi-60b was never determined. We were only able to determine the stereochemistry of 59b after Alloc removal, cyclization, and reduction to (–)-thionuphlutine (2c) through comparison to literature data. See:
For selected examples of ester reductions with i-Bu2AlH to form hemiaminals, see:
Once again, the thiaspirane stereochemistry in compounds 68a, 68b, 61a, and 62b was determined following conversion to the natural products 1b, 1c, 2b, and 2c through comparison to literature spectral and optical rotation data. See: