An Expedient Entry into the α-Mercaptodiketopiperazine Nucleus

Stephen T. Hilton; William B. Motherwell; David L. Selwood

doi:10.1055/s-2004-834823

LETTER

An Expedient Entry into the α-Mercaptodiketopiperazine Nucleus

Stephen T. Hilton^a, William B. Motherwell*^a, David L. Selwood^b
^a Chemistry Department, Christopher Ingold Laboratories, University College London, 20 Gordon Street, London, WC1H OAJ, UK
^b The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, UK
Fax: +44(20)76797524; e-Mail: w.b.motherwell@ucl.ac.uk;

Abstract

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Abstract

A novel approach to the α-mercaptodiketopiperazine nucleus is reported, which involved a three-component reaction of a number of amines with ethyl glyoxalate and para-methoxybenzylmercaptan. The subsequent products were readily elaborated to the monothiodiketopiperazine core structure.

Key words

epidithiodiketopiperazine - multicomponent reactions - thiols - imines - sulfur

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References

<A NAME="RD22604ST-1A">1a</A> Waring P. Beaver J. Gen. Pharmacol. 1996, 27: 1311

<A NAME="RD22604ST-1B">1b</A> Chai CLL. Waring P. Redox Report 2000, 5: 257

<A NAME="RD22604ST-1C">1c</A> Waring P. Eichner RD. Med. Res. Reviews 1988, 8: 499

<A NAME="RD22604ST-1D">1d</A> Johnson JR. Bruce FW. Dutcher JD. J. Am. Chem. Soc. 1943, 65: 2005

<A NAME="RD22604ST-2">2</A> Eichner RD. Waring P. Geue AM. Braithwaite AW. Müllbacher A. J. Biol. Chem. 1988, 263: 3772

<A NAME="RD22604ST-3">3</A> Chai CLL. Heath GA. Huleatt PB. O’Shea GA. J. Chem. Soc., Perkin Trans. 2 1999, 389

<A NAME="RD22604ST-4">4</A> Chai CLL. Elix JA. Huleatt PB. Tetrahedron Lett. 2003, 44: 263

<A NAME="RD22604ST-5">5</A> Moody CJ. Slawin AMZ. Willows D. Org. Biomol. Chem. 2003, 1: 2716

<A NAME="RD22604ST-6">6</A> Fukuyama T. Kishi Y. J. Am. Chem. Soc. 1976, 98: 6723

<A NAME="RD22604ST-7">7</A> Fukuyama T. Nakatsuka S. Kishi Y. Tetrahedron 1981, 37: 2045

<A NAME="RD22604ST-8">8</A> Trown PW. Biochem. Biophys. Res. Commun. 1968, 33: 402

<A NAME="RD22604ST-9">9</A> Herscheid JDM. Nivard RJF. Tijhus MW. Ottenheijm HCJ. J. Org. Chem. 1980, 45: 1885

<A NAME="RD22604ST-10">10</A> Herscheid JDM. Nivard RJF. Tijhus MW. Scholten HPH. Ottenheijm HCJ. J. Org. Chem. 1980, 45: 1880

<A NAME="RD22604ST-11">11</A> Hino T. Sato T. Tetrahedron Lett. 1971, 12: 3127

<A NAME="RD22604ST-12">12</A> Ottenheijm HCJ. Kerkhoff GPC. Bijen JWHA. J. Chem. Soc., Chem. Commun. 1975, 768

<A NAME="RD22604ST-13">13</A> Ottenheijm HCJ. Herscheid JDM. Kerkhoff GPC. Spande TF. J. Org. Chem. 1976, 41: 3433

<A NAME="RD22604ST-14">14</A> Ohler E. Tataruch F. Schmidt U. Chem. Ber. 1973, 106: 396

<A NAME="RD22604ST-15">15</A> Williams RM. Rastetter WH. J. Org. Chem. 1980, 45: 2625

<A NAME="RD22604ST-16">16</A> Miknis GF. Williams RM. J. Am. Chem. Soc. 1993, 115: 536

<A NAME="RD22604ST-17">17</A> Wu Z. Williams LJ. Danishefsky SJ. Angew. Chem. Int. Ed. 2000, 39: 3866

<A NAME="RD22604ST-18">18</A> Yaouancq L. René L. Dau M. Badet B. J. Org. Chem. 2002, 67: 5408

Representative Procedure: Benzylamine (2.75 mL, 2.70 g, 25.22 mmol) was added to a solution of ethyl glyoxalate (5.00 mL of a 50% solution in toluene, 25.22 mmol) in toluene (40 mL). This was followed 2 min afterwards by the addition of p-methoxybenzylmercaptan (3.51 mL, 3.89 g, 25.22 mmol) and the resulting cloudy solution left to stir at r.t. for 2 h. Organic solvent was removed by rotary evaporation at a bath temperature of less than 55 °C to give a yellow oil that was purified by flash column chromatography to give the protected α-mercapto amino acid ester as a colourless oil (8.01 g, 92%). MS (FAB⁺): C₁₉H₂₄NO₃S requires [M + H]: 346.14819. Found: [M⁺] 346.14768. IR (film): ν_max = 3347.2, 1732.0, 1511.1, 1301.9,1250.8, 1175.5, 1032.8 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.31 (3 H, t, J = 7.2 Hz, CO₂CH₂CH ₃), 3.72 (1 H, d, J = 13.1 Hz, SCH ₂), 3.75 (2 H, m, NHCH ₂), 3.79 (3 H, s, OCH ₃), 3.87 (1 H, d, J = 13.1 Hz, SCH ₂), 4.22 (2 H, q, J = 7.2 Hz, CO₂CH ₂CH₃), 4.35 (1 H, s, CH), 6.84 (2 H, d, J = 8.7 Hz, Ar-H), 7.23-7.29 (7 H, m, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.15 (CO₂CH₂ CH₃), 33.23 (SCH₂), 49.22 (NHCH₂), 55.28 (OCH₃), 61.41 (CO₂ CH₂CH₃), 63.71 (CH), 114.00 (Ar-C-H), 127.19 (Ar-C-H), 128.41 (Ar-C-H), 128.48 (Ar-C-H), 130.07 (Ar-C-H), 130.07 (quaternary C), 138.79 (quaternary C), 158.76 (quaternary C), 169.97 (CO₂CH₂CH₃). MS: m/z (%) = 346 (49) [M + H], 214 (31), 192 (100), 165 (30).

<A NAME="RD22604ST-20">20</A> Zoller U. Ben-Ishai D. Tetrahedron 1975, 31: 863

<A NAME="RD22604ST-21">21</A> Schouteeten A. Christidis Y. Mattioda G. Bull. Soc. Chim. Fr. 1978, 248

<A NAME="RD22604ST-22">22</A> Bock MG. Dipardo RM. Freidinger RM. J. Org. Chem. 1986, 51: 3718

<A NAME="RD22604ST-23">23</A> Ben-Ishai D. Altman J. Bernstein Z. Tetrahedron 1977, 33: 1191

<A NAME="RD22604ST-24">24</A> Weigl M. Wünsch B. Tetrahedron 2002, 58: 1173

<A NAME="RD22604ST-25">25</A> Baldwin JE. Bradley M. Adlington RM. Norris WJ. Turner NJ. Tetrahedron 1991, 47: 457

<A NAME="RD22604ST-26">26</A> Liu X. Reese CB. J. Chem. Soc., Perkin Trans. 1 2000, 2227

<A NAME="RD22604ST-27">27</A> Ino A. Hasegawa Y. Murabayashi A. Tetrahedron 1999, 55: 10283