PDF icon PDF herunterladen
Synlett 2009(12): 1959-1963  
DOI: 10.1055/s-0029-1217541
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Highly Diastereoselective 1,3-Dipolar Cycloaddition of a d-Galactose-Derived Nitrone with Dimethyl Maleate: Synthesis of Polyhydroxylated Perhydroaza­azulenes

Omprakash P. Bandea, Vrushali H. Jadhava, Vedavati G. Puranikb, Dilip D. Dhavale*a
a Garware Research Centre, Department of Chemistry, University of Pune, Pune 411 007, India
Fax: +91(20)25691728; e-Mail: ddd@chem.unipune.ernet.in;
b Center for Materials Characterization, National Chemical Laboratory, Pune 411 008, India
Weitere Informationen

Publikationsverlauf

Received 26 February 2009
Publikationsdatum:
03. Juli 2009 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik
Preview

Abstract

An intermolecular 1,3-dipolar cycloaddition of a d-­galactose-derived nitrone with dimethyl maleate was found to be perfectly diastereoselective at the nitrone carbon to give exclusive formation of isoxazolidine. The N-O bond reductive cleavage in isoxazolidine followed by lactam reduction afforded a pyrrolidine ring skeleton with sugar appendage that on acetonide cleavage and reductive amino-cyclization gave hitherto unknown hydroxy­methyl-substituted hexa- and pentahydroxy perhydroazaazulenes.

Key words

1,3-dipolar nitrone olefin cycloaddition (DNOC) - ­nitrone - iminosugars - inhibitors - diastereoselectivity

16

The ¹H NMR spectrum of crude compound obtained from evaporation of toluene, showed additional signals (<7%) corresponding to unreacted dimethyl maleate. However, no other signals corresponding to other diastereomers were detected.

17

All new compounds have been characterised by IR, ¹H NMR, ¹³C NMR, and elemental analysis. Selected Procedure and Analytical Data for Compound 5 A solution of nitrone 4 [¹4] (2.0 g, 5.5 mmol) and dimethyl maleate (2.3 g, 16.5 mmol) in toluene (20 mL) was stirred under nitrogen atmosphere at r.t. for 5 h. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (n-hexane-EtOAc = 85:15) to afford cycloadduct as a white solid (2.5 g, 89%); mp 99-101 ˚C; R f = 0.7 (hexane-EtOAc = 6:4); [α]D ²5 -83.5 (c 0.3, CHCl3). IR (KBr): 1753, 1728, 1494
cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.22 (s, 3 H), 1.30 (s, 3 H), 1.35 (s, 3 H), 1.50 (s, 3 H), 3.62 (dd, J = 8.1, 1.5 Hz, 1 H), 3.96 (s, 3 H), 3.99 (s, 3 H), 3.93-4.30 (m, 2 H), 4.17 (d, J = 13.5 Hz, 1 H), 4.27 (dd, J = 4.8, 1.8 Hz, 1 H), 4.33 (dd, J = 7.8, 1.5 Hz, 1 H), 4.40 (d, J = 13.5 Hz, 1 H), 4.55 (dd, J = 7.8, 1.8 Hz, 1 H), 4.73 (d, J = 8.4 Hz, 1 H), 5.51 (d, J = 4.8 Hz, 1 H), 7.18-7.37 (m, 3 H) 7.38-7.47 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 24.0, 24.8, 25.7, 26.1, 52.3, 52.4, 53.5, 61.9, 67.0, 67.5, 70.53, 70.59, 70.6, 78.9, 96.3, 108.4, 108.9, 127.0, 128.0 (s), 129.2 (s), 137.4, 169.4, 171.1. Anal. Calcd for C25H33NO10: C, 59.16; H, 6.55. Found: C, 59.29; H, 6.42.
Analytical Data for Compound 6
Viscous oil; 85%. R f = 0.5 (EtOAc); [α]D ²5 -69.77 (c 0.45, CHCl3). IR (neat): 3540-3200, 1734, 1687, 1438 cm-¹. ¹H NMR (300 MHz, CDCl3 + D2O): δ = 1.20 (s, 3 H), 1.30 (s, 3 H), 1.40 (s, 3 H), 1.60 (s, 3 H), 3.45 (t, J = 5.7 Hz, 1 H), 3.63 (s, 3 H), 3.92-4.16 (m, 4 H), 4.28 (dd, J = 5.4, 2.1 Hz, 1 H), 4.37 (d, J = 5.7 Hz, 1 H), 4.53 (dd, J = 7.8, 2.1 Hz, 1 H), 5.21 (d, J = 15.6 Hz, 1 H), 5.56 (d, J = 5.4 Hz, 1 H), 7.10-7.40 (m, 5 H). ¹³C NMR (75 MHz, CDCl3): δ = 23.9, 24.5, 25.4, 26.1, 43.6, 47.1, 52.1, 57.4, 63.2, 70.2, 70.8, 70.9, 72.5, 96.4, 108.1, 109.2, 127.4, 127.5 (s), 128.6 (s), 134.9, 172.5, 172.7. Anal. Calcd for C24H31NO9: C, 60.37; H, 6.54. Found: C, 60.25; H, 6.40. Analytical Data for Compound 7
White solid; 67%; mp 138-140 ˚C; R f = 0.3 (EtOAc); [α]D ²5 -48.80 (c 0.25, CHCl3). IR (KBr): 3600-3250, 1632, 1454 cm-¹. ¹H NMR (300 MHz, CDCl3 + D2O): δ = 1.38 (s, 6 H), 1.43 (s, 3 H), 1.46 (s, 3 H), 2.36 (dd, J = 9.9, 3.3 Hz, 1 H), 2.70-2.80 (m, 1 H), 2.82 (br d, J = 9.9, 1 H), 2.94 (t, J = 2.1 Hz, 1 H) 3.31 (t, J = 10.2 Hz, 1 H), 3.45 (d, J = 13.5 Hz, 1 H), 3.72 (dd, J = 10.2, 6.3 Hz, 1 H), 3.77 (d, J = 3.3 Hz, 1 H), 3.95 (br s, 1 H), 4.10 (d, J = 13.5 Hz, 1 H), 4.29-4.38 (m, 2 H), 4.64 (dd, J = 8.4, 2.4 Hz, 1 H), 5.64 (d, J = 5.1 Hz, 1 H), 7.15-7.40 (m, 5 H). ¹³C NMR (75 MHz, CDCl3): δ = 24.0, 24.9, 25.7, 26.2, 50.2, 58.5, 58.9, 64.5, 65.6, 67.3, 70.4, 71.0, 72.2, 72.9, 96.5, 108.6, 109.2, 126.7, 128.0 (s), 128.2 (s), 138.9. Anal. Calcd for C23H33NO7: C, 63.43; H, 7.64. Found: C, 63.57; H, 7.79.
Analytical Data for Compound 8
Viscous oil; 80%; R f = 0.4 (EtOAc); [α]D ²5 -63.76 (c 0.25, CHCl3). IR (neat): 3600- 3200, 1687, 1415 cm-¹. ¹H NMR (300 MHz, CDCl3 + D2O): δ = 1.22 (s, 3 H), 1.28 (s, 3 H), 1.39 (s, 3 H), 1.44 (s, 3 H), 2.90 (t, J = 7.2 Hz, 1 H), 3.41 (t, J = 9.0 Hz, 1 H), 3.48-3.58 (m, 2 H), 3.63 (dd, J = 10.5, 6.6 Hz, 1 H), 3.97 (br s, 1 H), 4.03 (s, 1 H), 4.30 (dd, J = 4.8, 2.1 Hz, 1 H), 4.39 (d, J = 7.8 Hz, 1 H), 4.46 (s, 1 H), 4.60 (d, J = 7.8 Hz, 1 H), 5.07 (ABq, J = 12.6 Hz, 2 H), 5.54 (d, J = 4.8 Hz, 1 H), 7.18-7.40 (m, 5 H). ¹³C NMR (75 MHz, CDCl3): δ = 24.0, 25.0, 25.6, 25.7, 49.1, 55.0, 61.5, 63.3, 66.71, 66.78, 70.4, 70.8, 72.1, 72.2, 96.2, 109.3, 109.4, 127.5, 127.7 (s), 128.2 (s), 136.4, 155.3. Anal. Calcd for C24H31NO9: C, 60.37; H, 6.54. Found: C, 60.59; H, 6.32.
Analytical Data for Compound 3a
Viscous oil; 80%; R f = 0.25 (MeOH); [α]D ²5 +45.01 (c 0.25, MeOH). IR (neat): 3676-3250 cm-¹. ¹H NMR (300 MHz, D2O): δ = 2.19 (m, 1 H), 2.81 (dd, J = 9.9, 2.7 Hz, 1 H), 3.13 (t, J = 9.0 Hz, 1 H), 3.27 (dd, J = 9.0, 6.9 Hz, 1 H), 3.61-3.78 (m, 2 H), 3.93 (dd, J = 9.9, 4.5 Hz, 1 H), 4.09 (d, J = 4.5 Hz, 1 H), 4.18-4.28 (m, 3 H), 4.94 (d, J = 6.0 Hz, 1 H). ¹³C NMR (75 MHz, D2O): δ = 53.8, 55.7, 60.1, 62.9, 66.9, 72.5, 75.6, 79.3, 84.6, 88.6. Anal. Calcd for C10H19NO7: C, 45.29; H, 7.22. Found: C, 49.31; H, 7.30.
Analytical Data for Compound 3b
Viscous oil; 92%. R f = 0.30 (MeOH). [α]D ²5 -3.0 (c 0.5, MeOH). IR (neat): 3670-3260 cm-¹. ¹H NMR (300 MHz, D2O): δ = 2.51 (br d, J = 5.4 Hz, 1 H), 3.02 (br s, 1 H), 3.15 (br s 1 H), 3.35 (br s, 1 H), 3.53 (br d, J = 11.1 Hz, 1 H), 3.61 (dd, J = 11.7, 7.2 Hz, 1 H), 3.70-3.85 (m, 2 H), 3.86-4.06 (m, 2 H), 4.11 (d, J = 7.2 Hz, 1 H), 4.29 (br d, J = 5.4 Hz, 1 H), 4.39 (s, 1 H). ¹³C NMR (75 MHz, D2O): δ = 49.0, 55.3, 61.6 (s), 63.5, 66.8, 69.3, 71.3, 73.0, 74.2. Anal. Calcd for C10H19NO6: C, 48.19; H, 7.68. Found: C, 48.30; H, 7.91.