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Synlett 2003(4): 0522-0526
DOI: 10.1055/s-2003-37506
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Convergent Approach to Biphenomycin Antibiotics

Franz F. Paintner*a, Klaus Görlera, Wolfgang Voelterb
a 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;
b Abteilung für Physikalische Biochemie, Physiologisch-chemisches Institut der Universität Tübingen, Hoppe-Seyler-Straße 4, 72076 Tübingen, Germany
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Publication History

Received 10 January 2003
Publication Date:
26 February 2003 (online)

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Abstract

A new, convergent approach to the biaryl key intermediate of Schmidt’s biphenomycin B total synthesis has been accomplished via a palladacycle complex catalyzed Stille cross-coupling of two o-tyrosine building blocks.

Key words

biphenomycins - antibiotics - cyclopeptides - asymmetric synthesis - Stille coupling

    References

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8

Benzylbromide 8 was prepared from 5-iodo-salicylic acid in 40% overall yield as indicated in Scheme [6] .

9

( S )-2-Amino-3-(2-benzyloxy-5-iodophenyl)propionic acid(11): Colourless crystals, mp 228-230 °C (decomp.). [α]D 20 = -11.8 (c 0.11, MeOH); 1H NMR (500 MHz, CD3OD): δ = 2.89 (dd, J = 9.2/14.3 Hz, 1 H, CH 2CH), 3.41 (dd, J = 4.7/14.3 Hz, 1 H, CH 2CH), 3.89 (dd, J = 4.7/9.2 Hz, 1 H, CH2CH), 5.18 (s, 2 H, OCH2), 6.86 (d, J = 8.6 Hz, 1 H, Harom), 7.28-7.49 (m, 5 H, Harom), 7.54 (dd, J = 2.2/8.6 Hz, 1 H, Harom), 7.57 (d, J = 2.2 Hz, 1 H, Harom); 13C NMR (125 MHz, CD3OD): δ = 33.5, 56.2, 71.3, 83.9, 115.9, 128.7, 128.9, 129.2, 129.8, 138.2, 138.8, 141.0, 158.3, 173.6; MS (MALDI): m/z = 398 [M + 1]. HRMS (CI, CH5 +): Anal. Calcd for C16H16NO3I (M + H+): 398.0253; Found: 398.0253.

18

In addition to 20, 21 and 22 small amounts of the respective aryl iodide homocoupling product i (1-7%) and in case of entries 1-4 product ii (3-6%), which arises from aryl transfer by the arsine, were also obtained (Figure [2] ).

21

Stille coupling of 5b and 6: A solution of 5b (29.5 mg, 37 mol) in degassed NMP (0.14 mL) was added to a stirred mixture of anhydrous LiCl (4.3 mg, 102 mol), 6 (20.0 mg, 34 mol) and 23 (1.6 mg, 1.7 mol) in degassed NMP (0.2 mL) at room temperature. The reaction mixture was heated at 90 °C for 14 h. After cooling to room temperature, the reaction mixture was diluted with CH2Cl2 and filtered through a pad of silica gel. The filtrate was washed with aqueous 1.3 M phosphate buffer pH 7.0 and water, dried (MgSO4) and concentrated under reduced pressure. The resulting residue was purified by prep. HPLC (LiChrosorb® Si 60 5 µm, n-heptane-EtOAc, 85:15) to give 20.9 mg (64%) 3 as a colourless solid.
3: [α]D 20 = +10.3 (c = 0.95, CHCl3); lit. [5a] : [α]D = +11.2. 1H NMR (500 MHz, CDCl3) δ = -0.03 [s, 9 H, Si(CH3)3], 0.85-0.91 (m, 2 H, CH2CH 2Si), 1.35 [s, 9 H, C(CH3)3], 3.06-3.14 (m, 2 H, CHCH 2), 3.18-3.26 (m, 2 H, CHCH 2), 4.05-4.21 (m, 2 H, CH 2CH2Si), 4.56-4.67 (m, 2 H, CHCH2), 4.95-5.17 (m, 8 H, OCH2Ph), 5.38 (d, 1 H, J = 7.8 Hz, NHBoc), 5.61 (d, 1 H, J = 7.7 Hz, NHZ), 6.91 (d, 1 H, J = 8.6 Hz, Harom), 6.94 (d, 1 H, J = 8.6 Hz, Harom), 7.19-7.38 (m, 20 H, Harom.), 7.42-7.48 (m, 4 H, Harom).