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Synlett 2003(7): 1022-1024
DOI: 10.1055/s-2003-39287
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of an Isomer of the Oxaspirobicyclic Tetronic Acid Unit of the CCK-B Receptor Antagonist Tetronothiodin

Philip C. Bulman Page*a, Hooshang Vahedi, Kevin J. Batchelor, Stephen J. Hindley, Mark Edgar, Paul Beswickb
a Department of Chemistry, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK
Fax: +44(1509)223926; e-Mail: p.c.b.page@lboro.ac.uk;
b Department of Medicinal Chemistry, Neurology & GI Centre of Excellence for Drug Discovery, Glaxo SmithKline, Medicines Research Centre, Gunnells Wood Road, Stevenage, Herts SG2 2NY
Further Information

Publication History

Received 10 February 2003
Publication Date:
20 May 2003 (online)

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Abstract

An isomer of the oxaspirobicyclic tetronic acid unit of the CCK-B Receptor antagonist tetronothiodin, diastereoisomeric at the spiro centre, has been synthesized in five steps from dienol 4.

Key words

tetronothiodin - Diels-Alder - Dieckmann - spiro tetronic acid - CCK

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7

The stereochemical assignment for diene 4 was based on the coupling constant between H-3 and H-4 (J = 18 Hz), consistent with the E isomer.

8

Triene 9 was prepared in 82% yield by reaction of alcohol 4 with diphenylvinylsilyl chloride in dichloromethane at r.t. in the presence of triethylamine.

9

The stereochemical assignment for lactol 10 was based on NOE data and on the coupling constant between the hydrogen atoms at the ring junction positions (J = 4.5 Hz), consistent with the cis isomer.

15

Analytical data: IR(neat): νmax = 3378, 2923, 1782, 1613
cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.74-0.84 (1 H, m), 1.1 (3 H, d, J = 5.2 Hz), 1.19 (1 H, s), 1.31 (3 H, t, J = 8.0 Hz), 1.41-1.49 (1 H, m), 1.60 (3 H, s), 1.76-1.79 (2 H, m), 1.97-2.03 (1 H, m), 2.33-2.40 (2 H, m), 3.59-3.71 (2 H, m), 4.3 (2 H, q, J = 8.0 Hz), 5.3 (1 H, s). 13C NMR (100.6 MHz, CDCl3): δ = 194, 167, 166, 138, 121, 95, 85, 62, 60, 41, 36, 35, 31, 23, 19, 15. MS (EI): m/z (%) = 310 (100) [M+] , 199, 134, 120, 91, 60. Found: 310.14124; C16H22O6 requires 310.14164.