A Convergent Synthesis of the C31-C46 Fragment of Phorboxazoles

J. S. Yadav; G. Rajaiah

doi:10.1055/s-2004-829572

LETTER

A Convergent Synthesis of the C31-C46 Fragment of Phorboxazoles [1]

J. S. Yadav*, G. Rajaiah
Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: +91(40)27160512; e-Mail: yadav@iict.ap.nic.in;

Abstract

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Abstract

A convergent synthesis of the C31-C46 fragment of phorboxazoles has been achieved. This involved the preparation of a C31-C39 aldehyde and a C40-C46 benzothiazole secondary sulfone followed by their coupling, employing modified Julia olefination as a key reaction.

Key words

phorboxazole - Julia olefination - secondary sulfone - sodium formate

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References

IICT Communication No. 030704.

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Spectral data for the key fragments: Compound 3 (E:Z mixture): ¹H NMR (200 MHz, CDCl₃): δ = 6.61 (d, J = 17.3 Hz, 1 H), 6.27-6.02 (m, 5 H), 5.61-5.42 (m, 2 H), 5.37-5.24 (m, 2 H), 4.58-4.36 (m, 6 H), 4.14 (q, J = 14.1 Hz, 4 H), 3.72-3.45 (m, 6 H), 3.34 (s, 6 H), 3.31 (s, 6 H), 3.24 (s, 6 H), 3.23 (s, 6 H), 2.66 (dd, J = 14.1 Hz, 4.6 Hz, 4 H), 2.44-2.22 (m, 6 H), 1.90 (s, 3 H), 1.83 (s, 3 H), 1.69-1.55 (m, 2 H), 1.41-1.19 (m, 10 H). IR (neat): 2926, 1736, 1619, 1418, 1376, 1207, 1146, 1089, 1033 cm^-1. FAB-MS: m/z = 536
[M + 1].
[α]_D = -19.8 (c 0.5, CHCl₃).
Compound 4 (mixture of diastereomers): ¹H NMR (200 MHz, CDCl₃): δ = 8.22-8.18 (m, 2 H), 8.02-7.96 (m, 2 H), 7.67-7.53 (m, 4 H), 6.02-5.44 (m, 8 H), 4.36-4.23 (m, 2 H), 3.56-3.46 (m, 2 H), 3.16 (s, 3 H), 3.02 (s, 3 H), 2.14-1.95 (m, 4 H), 1.64-1.56 (m, 6 H). IR (neat): 2926, 1701, 1469, 1325, 1145, 1093 cm^-1. FAB-MS: m/z = 418 [M + 2].
[α]_D = -8.20 (c 0.8, CHCl₃).
Compound 6: ¹H NMR (200 MHz, CDCl₃): δ = 7.25 (d, J = 8.8 Hz, 2 H), 6.81 (d, J = 8.8 Hz, 2 H), 4.45 (Abq, J = 12.3 Hz, 2 H), 3.81 (s, 3 H), 3.69-3.63 (dd, J = 12.5, 6.0 Hz, 1 H), 3.45-3.34 (dd, J = 12.5, 6.0 Hz, 1 H), 3.23-3.18 (m, 1 H), 2.76-2.69 (dd, J = 12.3, 5.9 Hz, 1 H), 2.57-2.54 (dd, J = 12.3, 5.9 Hz, 1 H). IR (neat): 2922, 1512, 1245
cm^-1. MS (EI): m/z = 194 [M⁺].
[α]_D = +3.1 (c 1.5, CHCl₃).
Compound 10: ¹H NMR (200 MHz, CDCl₃): δ = 6.64-6.49 (m, 1 H), 6.32-6.08 (m, 3 H), 3.93-3.70 (m, 1 H), 3.29 (s, 3 H), 2.58-2.46 (m, 1 H), 2.38-2.26 (m, 1 H), 2.22 (s, 3 H). IR (neat): 2932, 1735, 1612, 1310 cm^-1. MS (EI): m/z = 233 [M⁺].
[α]_D = +2.9 (c 0.6, CHCl₃).
Compound 12: ¹H NMR (200 MHz, CDCl₃): δ = 7.18 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 4.40 (s, 2 H), 3.81 (s, 3 H), 3.58-3.53 (m, 2 H), 3.06-2.96 (m, 1 H), 2.76-2.72 (m, 1 H), 2.50-2.43 (m, 1 H), 1.89-1.78 (m, 1 H), 1.72-1.60 (m, 1 H). IR (neat): 2845, 1612, 1513 cm^-1. MS (EI): m/z = 208 [M⁺].
[α]_D = +14.4 (c 1.0, CHCl₃).
Compound 15: ¹H NMR (200 MHz, CDCl₃): δ = 7.22 (d, J = 8.6 Hz, 2 H), 6.84 (d, J = 8.6 Hz, 2 H), 5.80-5.57 (m, 2 H), 4.40 (s, 2 H), 4.00 (d, J = 7.2 Hz, 2 H), 3.79 (s, 3 H), 3.55-3.45 (m, 2 H), 3.40-3.36 (m, 1 H), 3.31 (s, 3 H), 2.34-2.18 (m, 2 H), 1.74-1.68 (m, 2 H). IR (neat): 2935, 1608, 1513, 1252 cm^-1. FAB-MS: m/z = 298 [M + 1].
[α]_D = -17.6 (c 0.75, CHCl₃).
Compound 17: ¹H NMR (200 MHz, CDCl₃): δ = 4.09-3.93 (m, 1 H), 3.88-3.71 (m, 3 H), 3.66-3.55 (m, 3 H), 3.41 (s, 3 H), 1.96-1.94 (m, 2 H), 1.77-1.63 (m, 2 H), 1.40 (s, 6 H). IR (neat): 3482, 2921, 1462 cm^-1. MS (EI): m/z = 252 [M⁺].
[α]_D = +12.2 (c 2.0, CHCl₃).
Compound 20: ¹H NMR (200 MHz, CDCl₃): δ = 4.17 (q, J = 6.7 Hz, 2 H), 3.98-3.88 (m, 1 H), 3.75-3.58 (m, 4 H), 3.38 (s, 3 H), 3.28 (s, 3 H), 2.68 (s, 2 H), 2.55-2.48 (m, 1 H), 2.38-2.15 (m, 2 H), 2.05-1.92 (m, 2 H), 1.28 (t, J = 6.7 Hz, 3 H). IR (neat): 3447, 2949, 1731, 1319, 1228 cm^-1.
FAB-MS: m/z = 279 [M - OMe].
[α]_D = -78.6 (c 1.0, CHCl₃).
Compound 23: ¹H NMR (200 MHz, CDCl₃): δ = 4.71 (Abq, J = 10.4 Hz, 2 H), 4.13 (q, J = 6.7 Hz, 2 H), 3.79-3.48 (m, 5 H), 3.41 (s, 3 H), 3.32 (s, 3 H), 3.21 (s, 3 H), 2.63 (Abq, J = 14.1 Hz, 2 H), 2.38-2.28 (m, 1 H), 1.98-1.88 (m, 1 H), 1.49-1.31 (m, 2 H), 1.27 (t, J = 6.7 Hz, 3 H). IR (neat): 3443, 2925, 1733, 1036 cm^-1. MS (EI): m/z = 336 [M⁺].
[α]_D = -19.2 (c 1.1, CHCl₃).