New Synthetic Approach to C5-Hydroxymethyl-Substituted Polyhydroxylated Pyrrolizidines

Daniela Beňadiková; Michal Medvecký; Alexandra Filipová; Ján Moncoľ; Milan Gembický; Naďa Prónayová; Robert Fischer

doi:10.1055/s-0033-1339123

Synlett, Table of Contents

Synlett 2014; 25(11): 1616-1620
DOI: 10.1055/s-0033-1339123

letter

New Synthetic Approach to C5-Hydroxymethyl-Substituted Polyhydroxylated Pyrrolizidines

Daniela Beňadiková

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk

,

Michal Medvecký

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk

,

Alexandra Filipová

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk

,

Ján Moncoľ

^bInstitute of Inorganic Chemistry, Technology and Materials, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic

,

Milan Gembický

^cBruker AXS Inc., 5465 East Cheryl Parkway, Madison, WI 53711-5373, USA

,

Naďa Prónayová

^dInstitute of Analytical Chemistry, Department of NMR Spectroscopy and Mass Spectrometry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic

,

Robert Fischer*

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk

› Author Affiliations

Abstract

All articles of this category

Abstract

A new approach to C5-hydroxymethyl-substituted pyrrolizidines involving 1,3-dipolar cycloaddition of a d-mannose-derived cyclic nitrone and the S_N-reaction of a silyl ketene acetal is presented. The synthesis shows good stereoselectivity as a result of the presence of a dioxolane substituent at C5 of the nitrone, the bulkiness of the silyl ketene acetal, and the shape of the pyrrolizidinylium intermediate formed during intramolecular reductive amination. This approach provides access to pyrrolizidines with the same relative configuration as that found in hyacinthacines C₂ and C₃, and in (+)-pochonicine.

Key words

carbohydrates - heterocycles - nitrones - pyrrolizidines - stereoselective synthesis

Full Text

References

References

1a Asano N, Kuroi H, Ikeda H, Kizu H, Kameda Y, Kato A, Adachi I, Watson AA, Nash RJ, Fleet GW. J. Tetrahedron: Asymmetry 2000; 11: 1
1b Asano N, Nash RJ, Molyneux RJ, Fleet GW. J. Tetrahedron: Asymmetry 2000; 11: 1645
1c Compain P, Martin OR. Bioorg. Med. Chem. 2001; 9: 3077
1d Watson AA, Fleet GW. J, Asano N, Molyneux RJ, Nash RJ. Phytochemistry 2001; 56: 265
1e Iminosugars: From Synthesis to Therapeutic Applications . Compain P, Martin OR. Wiley; Chichester: 2007
1f Asano N In Modern Alkaloids: Structure, Isolation, Synthesis and Biology: Fattorusso E. Taglialatela-Scafati O. Wiley-VCH; Weinheim: 2008
1g Winchester BG. Tetrahedron: Asymmetry 2009; 20: 645
1h Gloster TM, Davies GJ. Org. Biomol. Chem. 2010; 8: 305
1i Best D, Wang C, Weymouth-Wilson AC, Clarkson RA, Wilson FX, Nash RJ, Miyauchi S, Kato A, Fleet GW. J. Tetrahedron: Asymmetry 2010; 21: 311
1j Horne G, Wilson FX. Prog. Med. Chem. 2011; 50: 135
1k Nash RJ, Kato A, Yu C.-Y, Fleet GW. J. Future Med. Chem. 2011; 3: 1513
1l Gloster TM. Biochem. Soc. Trans. 2012; 40: 913 ; and references cited therein

2a Davis BJ. Tetrahedron: Asymmetry 2009; 20: 652
2b Tamayo JA, Franco F, Lo Re D, Sánchez-Cantalejo F. J. Org. Chem. 2009; 74: 5679
2c Affolter O, Baro A, Frey W, Laschat S. Tetrahedron 2009; 65: 6626
2d Ribes C, Falomir E, Carda M, Marco JA. Tetrahedron 2009; 65: 6965
2e Izquierdo I, Plaza M, Tamayo JA, Franco F, Sánchez-Cantalejo F. Tetrahedron 2010; 66: 3788
2f Tamayo JA, Franco F, Sánchez-Cantalejo F. Tetrahedron 2010; 66: 7262
2g Delso I, Tejero T, Goti A, Merino P. Tetrahedron 2010; 66: 1220
2h Ritthiwigrom T, Nash RJ, Pyne SG. Tetrahedron 2010; 66: 9340
2i Garrabou X, Gómez L, Joglar J, Gil S, Parella T, Bujons J, Clapés P. Chem. Eur. J. 2010; 16: 10691
2j Bonaccini C, Chioccioli M, Parmeggiani C, Cardona F, Lo Re D, Soldaini G, Vogel P, Bello C, Goti A, Gratteri P. Eur. J. Org. Chem. 2010; 5574
2k Brock EA, Davies SG, Lee JA, Roberts PM, Thomson JE. Org. Lett. 2011; 13: 1594
2l Tamayo JA, Franco F, Sánchez-Cantalejo F. Eur. J. Org. Chem. 2011; 7182
2m D’Adamio G, Goti A, Parmeggiani C, Moreno-Clavijo E, Robina I, Cardona F. Eur. J. Org. Chem. 2011; 7155
2n Gkizis P, Argyropoulos NG, Coutouli-Argyropoulou E. Tetrahedron 2013; 69: 8921
2o Martella D, Cardona F, Parmeggiani C, Franco F, Tamayo JA, Robina I, Moreno-Clavijo E, Moreno-Vargas AJ, Goti A. Eur. J. Org. Chem. 2013; 4047
2p Marjanovic J, Divjakovic V, Matovic R, Ferjancic Z, Saicic RN. Eur. J. Org. Chem. 2013; 5555
2q Rajender A, Rao JP, Rao BV. Eur. J. Org. Chem. 2013; 1749
2r Xu W.-Y, Iwaki R, Jia Y.-M, Zhang W, Kato A, Yu C.-Y. Org. Biomol. Chem. 2013; 11: 4622 ; and references cited therein

3a Kato A, Kato N, Adachi I, Hollinshead J, Fleet GW. J, Kuriyama C, Ikeda K, Asano N, Nash RJ. J. Nat. Prod. 2007; 70: 993
3b Sengoku T, Satoh Y, Takahashi M, Yoda H. Tetrahedron Lett. 2009; 50: 4937

4 Usuki H, Toyo-oka M, Kanzaki H, Okuda T, Nitoda T. Bioorg. Med. Chem. 2009; 17: 7248
5 Kitamura Y, Koshino H, Nakamura T, Tsuchida A, Nitoda T, Kanzaki H, Matsuoka K, Takahashi S. Tetrahedron Lett. 2013; 54: 1456
6 Zhu J.-S, Nakagawa S, Chen W, Adachi I, Jia Y.-M, Hu X.-G, Fleet GW. J, Wilson FX, Nitoda T, Horne G, van Well R, Kato A, Yu C.-Y. J. Org. Chem. 2013; 78: 10298

7a Fišera L In Heterocycles from Carbohydrate Precursors . El Ashry ES. H. Springer; Berlin: 2007: 287
7b Dugovič B, Fišera L, Reißig H.-U. Eur. J. Org. Chem. 2008; 277

8a Rehák J, Fišera L, Kožíšek J, Bellovičová L. Tetrahedron 2011; 67: 5762
8b Podolán G, Kleščíková L, Fišera L, Kožíšek J, Fronc M. Synlett 2011; 1668
8c Podolán G, Fišera L, Kožíšek J, Fronc M. Heterocycles 2012; 84: 683

9a Brandi A, Cardona F, Cicchi S, Cordero FM, Goti A. Chem. Eur. J. 2009; 15: 7808
9b Carmona AT, Whigtman RH, Robina I, Vogel P. Helv. Chim. Acta 2003; 86: 3066
9c Toyao A, Tamura O, Takagi H, Ishibashi H. Synlett 2003; 35
9d Cardona F, Parmeggiani C, Faggi E, Bonaccini C, Gratteri P, Sim L, Gloster TM, Roberts S, Davies GJ, Rose DR, Goti A. Chem. Eur. J. 2009; 15: 1627

10 Holzapfel CW, Crous R. Heterocycles 1998; 48: 1337

11a Fischer R, Drucková A, Fišera L, Hametner C. ARKIVOC 2002; (viii): 80
11b Fischer R, Stanko B, Prónayová N. Synlett 2013; 24: 2132
11c Fischer R, Lackovičová D, Fišera L. Synthesis 2012; 44: 3783

12a Narasaka K, Ichikawa Y.-i, Kubota H. Chem. Lett. 1987; 16: 2139
12b Ichikawa Y.-i, Kubota H, Fujita K, Okauchi T, Narasaka K. Bull. Chem. Soc. Jpn. 1989; 62: 845
12c Mukaiyama T, Uchiro H, Hirano N, Ishikawa T. Chem. Lett. 1996; 25: 629

13 Malhiac C, Tekin J, Ramiandrasoa G, Leveque H, Combret J.-C. Phosphorus, Sulfur Silicon Relat. Elem. 1995; 102: 127
14 Methyl (±)-(2-Benzyl-3-phenylisoxazolidin-5-yl)(dimethoxy)acetate (6a); Typical Procedure The reaction flask was charged with 5-acetoxyisoxazolidines 4a,b (1.13 g, 3.80 mmol), sealed with a rubber septum, and filled with argon. Anhydrous CH₂Cl₂ (8 mL) was added and the solution was cooled to –80 °C. Silyl ketene acetal 5 (1.57 g, 7.61 mmol) and TMSOTf (0.69 mL, 3.80 mmol) were added successively and the mixture was stirred at –80 °C for 1 h. When the starting material had disappeared (TLC; hexanes–EtOAc, 70:30), the reaction was quenched by adding sat. aq NaHCO₃ (10 mL). The mixture was allowed to warm to r.t., CH₂Cl₂ (10 mL) was added, and the mixture was vigorously stirred for 5 min. The organic layer was then separated and the aqueous layer was extracted with CH₂Cl₂ (2 × 10 mL). The organic layers were combined, washed with H₂O, dried (Na₂SO₄), filtered, and concentrated in vacuo. Column chromatography [silica gel, hexanes–EtOAc (80:20)] gave a colorless solid; yield: 0.95 g (2.56 mmol, 67%); mp 78–80 °C (hexanes); ¹H NMR (600 MHz, CDCl₃): δ = 2.63 (ddd, J = 12.8, 8.4, 7.1 Hz, 1 H, H-4_a), 2.75 (ddd, J = 12.8, 10.2, 7.0 Hz, 1 H, H-4_b), 3.28 (s, 3 H, OCH₃), 3.41 (s, 3 H, OCH₃), 3.61 (s, 3 H, OCH₃), 3.68–3.73 (m, 2 H, H-3, CH₂Ph), 3.94 (d, J = 14.5 Hz, 1 H, CH₂Ph), 4.52 (dd, J = 8.4, 7.0 Hz, 1 H, H-5), 7.17–7.41 (m, 10 H, Ph); ¹³C NMR (150.1 MHz, CDCl₃): δ = 39.8, 50.4, 50.8, 52.7, 59.2, 70.0, 76.8, 102.0, 127.0, 127.9 (2 C), 128.0, 128.6, 129.5, 136.9, 138.4, 167.9.
15 Tamura O, Toyao A, Ishibashi H. Synlett 2002; 1344

16a Masson G, Cividino P, Py S, Vallée Y. Angew. Chem. Int. Ed. 2003; 42: 2265
16b Kaliappan KP, Das P, Chavan ST, Sabharwal SG. J. Org. Chem. 2009; 74: 6266
16c Li X, Qin Z, Wang R, Chen H, Zhang P. Tetrahedron 2011; 67: 1792
16d Bandaru A, Kaliappan KP. Synlett 2012; 23: 1473
16e Fu Y, Liu Y, Chen Y, Hügel HM, Wang M, Huang D, Hu Y. Org. Biomol. Chem. 2012; 10: 7669
16f Kui EL, Kanazawa A, Poisson J.-F, Py S. Tetrahedron Lett. 2013; 54: 5103
16g Khangarot RK, Kaliappan KP. Eur. J. Org. Chem. 2013; 2692

17 Crystallographic Data Collection and Refinement X-ray data were collected on a Bruker Kappa APEX Ultra diffractometer with mirror-monochromated Cu Kα radiation with a rotating anode Nonius FR951 at 100 K. The structure was solved by direct methods using SHELXS-97 [see ref. 20a], refined by a full-matrix least-squares procedure with CRYSTALS [ver. 14.43; see ref. 20b], and drawn with the OLEX2 package [see ref. 20c]. The chirality of carbon atoms was confirmed by using the PLATON program [see ref. 20d] for C1(S), C3(S), C4(R), C5(S), C6(S), and C7(S). X-ray Data for C₁₆H₂₅NO₇ (8a) Monoclinic, space group, P2₁, a = 8.6080(5), b = 9.8526(6), c = 10.6718(6) Å, β = 103.018(2)°, V = 881.83(9) Å³, Z = 2; final R = 0.0255, R _w = 0.0657, S = 1.004, Flack parameter –0.03(12); maximum and minimum residual densities 0.15 and –0.15 eÅ^–3, respectively. Crystallographic data for compound 8a have been deposited with accession number CCDC 883297, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.
18 Methyl {(3aS,4S,7S,8aS,8bR)-4-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2,2-dimethylhexahydro[1,3]dioxolo[3,4]-pyrrolo[1,2-b]isoxazol-7-yl}(dimethoxy)acetate (9) Colorless oil; yield: 430 mg (69%); [α]_D ²⁰ +59.80 (c 0.99, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.29 (s, 6 H, 2 × CH₃), 1.34 (s, 3 H, CH₃), 1.47 (s, 3 H, CH₃), 2.62 (ddd, J = 12.8, 8.9, 1.3 Hz, 1 H, H-3_a), 2.81 (ddd, J = 13.0, 8.3, 5.5 Hz, 1 H, H-3_b), 3.30 (s, 3 H, OCH₃), 3.40 (s, 3 H, OCH₃), 3.77–3.68 (m, 2 H, H-6, H-3a), 3.82 (s, 3 H, OCH₃), 3.96 (d, J = 7.1 Hz, 2 H, H-5′_a,b), 4.24 (td, J = 7.1, 2.8 Hz, 1 H, H-4′), 4.42 (dd, J = 8.9, 5.5 Hz, 1 H, H-2), 4.66 (dd, J = 5.4, 6.1 Hz, 1 H, H-4), 4.82 (dd, J = 6.3, 1.4 Hz, 1 H, H-5). ¹³C NMR (150.1 MHz, CDCl₃): δ = 24.4, 25.0, 26.0, 26.5, 31.0, 50.3, 50.7, 52.9, 66.2, 69.6, 71.7, 76.4, 77.1, 83.1, 86.1, 101.8, 109.5, 112.9, 167.6.
19 (1S)-1-[(3aS,4S,6S,7S,8aS,8bR)-7-Hydroxy-6-(hydroxy-methyl)-2,2-dimethylhexahydro-4H-[1,3]dioxolo[4,5-a]-pyrrolizin-4-yl]ethane-1,2-diol (13): Selected NMR Data ¹H NMR (600 MHz, CDCl₃): δ = 1.35 (s, 3 H, CH₃), 1.57 (s, 3 H, CH₃), 2.06 (td, J = 14.1, 3.7 Hz, 1 H, H-7_b), 2.26 (ddd, J = 14.1, 7.7, 6.4 Hz, 1 H, H-7_a), 3.43 (dd, J = 10.5, 4.9 Hz, 1 H, H-5), 3.56 (dd, J = 9.7, 4.7 Hz, 1 H, H-1′), 3.64 (dd, J = 11.5, 4.7 Hz, 1 H, H-2′_a), 3.68 (d, J = 4.7 Hz, 1 H, H-3), 3.71 (dd, J = 11.5, 4.7 Hz, 1 H, H-2′_b), 3.82–3.87 (m, 2 H, H-7a, CH₂OH), 3.97 (dd, J = 12.3, 4.7 Hz, 1 H, CH₂OH), 4.35 (dd, J = 9.7, 5.0 Hz, 1 H, H-6), 4.59 (t, J = 5.2 Hz, 1 H, H-1), 4.73 (dd, J = 5.7, 1.3 Hz, 1 H, H-2). ¹³C NMR (150.1 MHz, CDCl₃): δ = 23.7, 25.5, 33.2, 61.0, 64.2, 65.3, 66.1, 66.6, 73.0, 74.0, 82.4, 86.9, 112.8.

20a Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112
20b Betteridge PW, Carruthers JR, Cooper RI, Prout K, Watkin DJ. J. Appl. Crystallogr. 2003; 36: 1487
20c Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JA. K, Puschmann H. J. Appl. Crystallogr. 2009; 42: 339
20d Spek AL. Acta Crystallogr., Sect. D 2009; 65: 148