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Synlett 2005(17): 2615-2618  
DOI: 10.1055/s-2005-917106
LETTER
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Sperabillin A and C

Lars Allmendinger, Gerd Bauschke, Franz F. Paintner*
Department Pharmazie - Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus C, 81377 München, Germany
Fax: +49(89)218077247; e-Mail: franz.paintner@cup.uni-muenchen.de;
Further Information

Publication History

Received 22 August 2005
Publication Date:
05 October 2005 (online)

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Abstract

The first total synthesis of sperabillin A and an improved total synthesis of sperabillin C have been achieved in 11 steps from N-Boc-O-methyl-l-tyrosine. The stereoselective pathway to the core (3R,5R)-3,6-diamino-5-hydroxyhexanoic acid involves an Arndt-Eistert homologation, an asymmetric Henry reaction and a ruthenium tetroxide-catalyzed oxidative degradation of a benzene ring as key steps.

Key words

sperabillins - antibiotics - pseudo-peptides - Henry reaction - ruthenium tetroxide

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10

The reaction of chiral aldehyde 6 with nitromethane in the presence of catalyst (+)-11 represents the matched case of double diastereoselection, since application of the enantiomeric catalyst (-)-11 gave the corresponding epimer of 5 with slightly lower stereoselectivity (91% de).

14

In the absence of sodium hydrogen carbonate a somewhat lower yield (56%) of product 10 was obtained.

15

Spectroscopic data of compound 4: [α]D 20 +20.8 (c 0.95 in CH2Cl2). 1H NMR (500 MHz, MeOH-d 4): δ = 0.13 (3 H, s), 0.15 (3 H, s), 0.92 (9 H, s), 1.43 (9 H, sbr), 1.78 (2 H, m), 2.31 (1 H, dd, J = 14.9, 7.7 Hz), 2.39 (1 H, dd, J = 14.9, 4.7 Hz), 3.01 (1 H, dd, J = 13.0, 4.1 Hz), 3.06 (1 H, dd, J = 13.0, 4.9 Hz), 3.85 (1 H, m), 4.18 (1 H, m), 4.09 (1 H, m). 13C NMR (100 MHz, MeOH-d 4): δ = -5.0, 18.4, 25.9, 28.3, 40.0, 43.5, 45.2, 45.8, 67.7, 79.6, 157.1, 178.6.

17

For an alternative stereoselective approach to (2E,4Z)-hexa-2,4-dienoic acid (14), see ref. 5b.

22

Spectroscopic data of sperabillin A (3a) [2c] : [α]D 23 -11.4 (c 0.4 in H2O), lit. [2c] [α]D 23 -11 (c 1.1 in H2O). 1H NMR (500 MHz, D2O): δ = 1.77 (1 H, ddd, J = 4.5, 10.0, 15.0 Hz), 1.87 (3 H, d, J = 7.2 Hz), 1.87 (1 H, m), 2.68 (2 H, t, J = 6.6 Hz), 2.74 (2 H, m), 3.33 (1 H, dd, J = 6.6, 14.0 Hz), 3.39 (1 H, dd, J = 4.5, 14.0 Hz), 3.55 (1 H, dt, J = 6.6, 14.0 Hz), 3.59 (1 H, dt, J = 6.7, 14.0 Hz), 3.86 (1 H, m), 4.00 (1 H, m), 6.02 (1 H, dq, J = 7.2, 10.8 Hz), 6.07 (1 H, d, J = 15.1 Hz), 6.23 (1 H, t, J = 10.8 Hz), 7.56 (1 H, dd, J = 11.8, 15.1 Hz). 13C NMR (100 MHz, D2O): δ = 16.0, 35.3, 38.0, 39.2, 39.8, 47.8, 49.1, 69.1, 125.1, 129.6, 139.4, 139.5, 171.7, 172.4, 174.7.

23

Spectroscopic data of sperabillin C (3c) [2c] : [α]D 23 -10.2 (c 0.4 in H2O), lit. [2c] [α]D 20 -11 (c 0.7 in H2O). 1H NMR (500 MHz, D2O): δ = 1.75 (1 H, ddd, J = 4.7, 10.0, 15.0 Hz), 1.83 (3 H, d, J = 5.5 Hz), 1.87 (1 H, ddd, J = 3.1, 7.5, 15.0 Hz), 2.67 (2 H, t, J = 6.7 Hz), 2.73 (2 H, d, J = 7.0 Hz), 3.30 (1 H, dd, J = 6.5, 14.0 Hz), 3.37 (1 H, dd, J = 4.7, 14.0 Hz), 3.57 (2 H, m), 3.85 (1 H, m), 3.98 (1 H, m), 5.97 (1 H, d, J = 15.5 Hz), 6.26 (2 H, m), 7.13 (1 H, dd, J = 9.7, 15.5 Hz). 13C NMR (100 MHz, D2O): δ = 20.7, 35.3, 38.0, 39.2, 39.8, 47.8, 49.1, 69.1, 122.9, 132.0, 143.2, 145.4, 171.6, 172.5, 174.7.