Microwave-Assisted, Solvent-Free Synthesis of Several Quinazoline Alkaloid Frameworks

Pilar Cledera; Juan Domingo Sánchez; Esmeralda Caballero; Tamara Yates; Elena G. Ramírez; Carmen Avendaño; M. Teresa Ramos; J. Carlos Menéndez

doi:10.1055/s-2007-990818

PAPER

Microwave-Assisted, Solvent-Free Synthesis of Several Quinazoline Alkaloid Frameworks

Pilar Cledera^a, Juan Domingo Sánchez^a, Esmeralda Caballero^a, Tamara Yates^b, Elena G. Ramírez^c, Carmen Avendaño^a, M. Teresa Ramos^a, J. Carlos Menéndez*^a
^a Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Fax: +34(913)941822; e-Mail: josecm@farm.ucm.es;
^b Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Casilla 237, Conceptión, Chile
^c Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México D. F. 04510, Mexico

Abstract

All articles of this category

Abstract

Microwave irradiation leads to a considerable improvement of the cyclocondensation between anthranilic acid and lactim ethers derived from piperazine-2,5-diones in terms of reaction times, yields, and stereocenter integrity. This reaction has been used to prepare some derivatives of the pyrazino[2,1-b]quinazoline-3,6-dione system present in many quinazoline alkaloids. It could also be applied to the synthesis of compounds containing the complete hexacyclic ring system of the anti-MDR natural product N-acetylardeemin, and other comprising the pentacyclic framework of circumdatin E. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino[2,1-b:5,4-b′]diquinazoline-8,16-dione in excellent yield.

Key words

microwave irradiation - lactim ether - alkaloids - antitumor agents - heterocycles

Full Text

References

For recent reviews, see:

<A NAME="RT09207SS-1A">1a</A> Avendaño C. Menéndez JC. Curr. Org. Chem. 2003, 7: 149

<A NAME="RT09207SS-1B">1b</A> Mhaske SB. Argade NP. Tetrahedron 2006, 62: 9788

<A NAME="RT09207SS-1C">1c</A> Eguchi S. Top. Heterocycl. Chem. 2006, 6: 113

<A NAME="RT09207SS-2">2</A> Ma Z. Hano Y. Nomura T. Chen Y. Heterocycles 1997, 46: 541

<A NAME="RT09207SS-3A">3a</A> Wong S.-M. Musza LL. Kydd GC. Kullnig R. Gillum AM. Cooper R. J. Antibiotics 1993, 46: 545

<A NAME="RT09207SS-3B">3b</A> Fujimoto H. Negishi E. Yamaguchi K. Nishi N. Yamazaki M. Chem. Pharm. Bull. 1996, 44: 1843

<A NAME="RT09207SS-4A">4a</A> Karwowski JP. Jackson M. Rasmussen RR. Humphrey PE. Poddig JB. Kohl WL. Scherr MH. Kadam S. McAlpine JB. J. Antibiotics 1993, 46: 374

<A NAME="RT09207SS-4B">4b</A> Hochlowski JE. Mullally MM. Spanton SG. Whittern DN. Hill P. McAlpine JB. J. Antibiotics 1993, 46: 380

<A NAME="RT09207SS-4C">4c</A> Chou TC. Depew KM. Zheng Y.-H. Safer ML. Chan D. Helfrich B. Zatorska D. Zatorski A. Bornmann W. Danishefsky SJ. Proc. Natl. Acad. Sci. U.S.A. 1998, 95: 8369

<A NAME="RT09207SS-5">5</A> Barrow CJ. Sun HH. J. Nat. Prod. 1994, 57: 471

<A NAME="RT09207SS-6">6</A> Rahbaek L. Breinholt J. Frisvad JC. Christophersen C. J. Org. Chem. 1999, 64: 1689

<A NAME="RT09207SS-7A">7a</A> Dallavalle S. Merlini L. Beretta GL. Tinelli S. Zuninob F. Bioorg. Med. Chem. Lett. 2004, 14: 5757

<A NAME="RT09207SS-7B">7b</A> Cagir A. Eisenhauer BM. Gao R. Thomas SJ. Hecht SM. Bioorg. Med. Chem. 2004, 12: 6287

For selected reviews of MDR reversors, see:

<A NAME="RT09207SS-8A">8a</A> Wiese M. Pajeva IK. Curr. Med. Chem. 2001, 8: 685

<A NAME="RT09207SS-8B">8b</A> Teodori E. Dei S. Scapecchi S. Gualtieri F. Farmaco 2002, 57: 385

<A NAME="RT09207SS-8C">8c</A> Avendaño C. Menéndez JC. Curr. Med. Chem. 2002, 9: 159

<A NAME="RT09207SS-8D">8d</A> Robert J. Jarry C. J. Med. Chem. 2003, 46: 4805

<A NAME="RT09207SS-8E">8e</A> Avendaño C. Menéndez JC. Med. Chem. Rev. Online 2004, 1: 419

<A NAME="RT09207SS-8F">8f</A> Seelig A. Gatlik-Landwojtowicz E. Mini-Rev. Med. Chem. 2005, 5: 135

<A NAME="RT09207SS-8G">8g</A> Pleban K. Ecker EF. Mini-Rev. Med. Chem. 2005, 5: 153

<A NAME="RT09207SS-8H">8h</A> Raub TJ. Molecular Pharmaceutics 2006, 3: 3

<A NAME="RT09207SS-9">9</A> The pyrazino[2,1-b]quinazoline-3,6-dione moiety of the ardeemins has been identified as the pharmacophore responsible for its MDR reversal activity, see: Avendaño C. Caballero E. Méndez-Vidal C. de Quesada AR. Menéndez JC. Lett. Drug Des. Discovery 2006, 3: 369 ; see also ref. 12b

<A NAME="RT09207SS-10">10</A> Chou T.-C, Bertino JR, Danishefsky SJ, and Kahan BD. inventors; US 6,355,639.

Fiscalins and related natural products, see:

<A NAME="RT09207SS-11A">11a</A> He F. Snider BB. Synlett 1997, 483

<A NAME="RT09207SS-11B">11b</A> Snider BB. Busuyek MV. Tetrahedron 2001, 57: 3301

<A NAME="RT09207SS-11C">11c</A> Snider BB. Zeng H. Org. Lett. 2000, 2: 4103

<A NAME="RT09207SS-11D">11d</A> Wang H. Ganesan A. J. Comb. Chem. 2000, 2: 186

<A NAME="RT09207SS-11E">11e</A> Cledera P. Avendaño C. Menéndez JC. J. Org. Chem. 2000, 65: 1743

<A NAME="RT09207SS-11F">11f</A> Hernández F. Lumetzberger A. Avendaño C. Söllhuber MM. Synlett 2001, 1387

<A NAME="RT09207SS-11G">11g</A> Snider BB. Zeng H. Org. Lett. 2002, 4: 1087

<A NAME="RT09207SS-11H">11h</A> Snider BB. Zeng H. J. Org. Chem. 2003, 68: 545 ; see also refs. 14, 15, and 22

Ardeemins, see:

<A NAME="RT09207SS-12A">12a</A> Marsden SP. Depew KM. Danishefsky SJ. J. Am. Chem. Soc. 1994, 116: 11143

<A NAME="RT09207SS-12B">12b</A> Depew KM. Marsden SP. Zatorska D. Zatorski A. Bornmann WG. Danishefsky SJ. J. Am. Chem. Soc. 1999, 121: 11953

Circumdatins and related natural products, see:

<A NAME="RT09207SS-13A">13a</A> Bock MG. Dipardo RM. Pitzenberger SM. Homnick CF. Springer JP. Freidinger RM. J. Org. Chem. 1987, 52: 1644

<A NAME="RT09207SS-13B">13b</A> He F. Foxman BM. Snider BB. J. Am. Chem. Soc. 1998, 120: 6417

<A NAME="RT09207SS-13C">13c</A> Sugimori T. Okawa T. Eguchi S. Kakehi A. Yashima E. Okamoto Y. Tetrahedron 1998, 54: 7997

<A NAME="RT09207SS-13D">13d</A> Snider BB. Busuyek MV. Tetrahedron 2001, 57: 3301

<A NAME="RT09207SS-13E">13e</A> Witt A. Bergman J. J. Org. Chem. 2001, 66: 2784

<A NAME="RT09207SS-13F">13f</A> Grieder A. Thomas AW. Synthesis 2003, 1707 ; see also ref. 26

<A NAME="RT09207SS-14A">14a</A> Wang H. Ganesan A. J. Org. Chem. 1998, 63: 2432

<A NAME="RT09207SS-14B">14b</A> Wang H. Ganesan A. J. Org. Chem. 2000, 65: 1022

<A NAME="RT09207SS-15A">15a</A> He F. Snider BB. J. Org. Chem. 1999, 64: 1397

<A NAME="RT09207SS-15B">15b</A> Snider BB. Zeng H. J. Org. Chem. 2003, 68: 545

<A NAME="RT09207SS-16">16</A> For a review, see: Eguchi S. ARKIVOC 2005, (ii): 98

<A NAME="RT09207SS-17A">17a</A> Rajappa S. Advani BG. Tetrahedron 1973, 29: 1299

<A NAME="RT09207SS-17B">17b</A> Rajappa S. Advani BG. J. Chem. Soc., Perkin Trans. 1 1974, 2122

<A NAME="RT09207SS-18">18</A> Caballero E. Avendaño C. Menéndez JC. Tetrahedron: Asymmetry 1998, 9: 3025

For representative reviews and books on the use of microwave irradiation in synthetic organic chemistry, see:

<A NAME="RT09207SS-19A">19a</A> Caddick S. Tetrahedron 1995, 51: 10403

<A NAME="RT09207SS-19B">19b</A> de la Hoz A. Díaz-Ortiz A. Moreno A. Langa F. Eur. J. Org. Chem. 2000, 22: 3659

<A NAME="RT09207SS-19C">19c</A> Perreux L. Loupy A. Tetrahedron 2001, 57: 9199

<A NAME="RT09207SS-19D">19d</A> Lidstrom P. Tierney J. Wathey B. Westman J. Tetrahedron 2001, 57: 9225

<A NAME="RT09207SS-19E">19e</A> Santagada V. Perissutti E. Caliendo G. Curr. Med. Chem. 2002, 9: 1251

<A NAME="RT09207SS-19F">19f</A> Microwaves in Organic Synthesis Loupy A. Wiley-VCH; Weinheim: 2002.

<A NAME="RT09207SS-19G">19g</A> Varma RS. Advances in Green Chemistry: Chemical Synthesis Using Microwave Irradiation AstraZeneca Research Foundation; India: 2002.

<A NAME="RT09207SS-19H">19h</A> Tierney J. Lindstrom P. Microwave Assisted Organic Synthesis Blackwell; Oxford: 2004.

<A NAME="RT09207SS-19I">19i</A> Hayes BL. Aldrichimica Acta 2004, 37: 66

<A NAME="RT09207SS-19J">19j</A> Kappe CO. Angew. Chem. Int. Ed. 2004, 43: 6250

<A NAME="RT09207SS-19K">19k</A> Tierney JP. Lidström P. Microwave Assisted Organic Synthesis Blackwell; Oxford: 2005.

<A NAME="RT09207SS-19L">19l</A> For a symposium-in-print on the subject, see: Tetrahedron 2006, 62: 4623

For precedent for microwave-assisted von Niementowski-type synthesis of quinazolines from thioimino ethers on a graphite support, although not derived from piperazinediones, see:

<A NAME="RT09207SS-20A">20a</A> Soukri M. Guillaumet G. Besson T. Aziane D. Aadil M. Essassi El M. Akssira M. Tetrahedron Lett. 2000, 41: 5857

<A NAME="RT09207SS-20B">20b</A> Domon L. LeCoeur C. Grelard A. Thiéry V. Besson T. Tetrahedron Lett. 2001, 42: 6671

<A NAME="RT09207SS-20C">20c</A> Alexandre FR. Berecibar A. Wrigglesworth R. Besson T. Tetrahedron 2003, 59: 1413

<A NAME="RT09207SS-21">21</A> Preliminary communication: Cledera P. Sánchez JD. Caballero E. Avendaño C. Ramos MT. Menéndez JC. Synlett 2004, 803

<A NAME="RT09207SS-22">22</A> For alternative routes to pyrazinoquinazoline alkaloids involving microwave-assisted reactions, see Liu J.-F. Ye P. Zhang B. Bi G. Sargent K. Yu L. Yohannes D. Baldino CM. J. Org. Chem. 2005, 70: 6339

Compound 1a: see ref. 17. Compounds 1b-d:

<A NAME="RT09207SS-23A">23a</A> López-Cobeñas A. Cledera P. Sánchez JD. Pérez-Contreras R. López-Alvarado P. Ramos MT. Avendaño C. Menéndez JC. Synlett 2005, 1158

<A NAME="RT09207SS-23B">23b</A> López-Cobeñas A. Cledera P. Sánchez JD. López-Alvarado P. Ramos MT. Avendaño C. Menéndez JC. Synthesis 2005, 3412

Compound 1e:

<A NAME="RT09207SS-23C">23c</A> Sánchez JD. Ramos MT. Avendaño C. Tetrahedron 1998, 54: 969

<A NAME="RT09207SS-24">24</A> Fukuyama T. Frank RK. Laird AA. Tetrahedron Lett. 1985, 26: 2955

<A NAME="RT09207SS-25">25</A> Cledera P. Avendaño C. Menéndez JC. Tetrahedron 1998, 54: 12349

<A NAME="RT09207SS-26">26</A> Gallina C. Liberatori A. Tetrahedron 1974, 30: 667

<A NAME="RT09207SS-27">27</A> For alternative routes to quinazolinobenzodiazepine alkaloids involving microwave-assisted reactions, see: Liu J.-F. Kaselj M. Isome Y. Chapnick J. Zhang B. Bi G. Yohannes D. Yu L. Baldino CM. J. Org. Chem. 2005, 70: 10488

<A NAME="RT09207SS-28">28</A> Eguchi S. Yamashita K. Matsuhita Y. Kakehi A. J. Org. Chem. 1995, 60: 4006

<A NAME="RT09207SS-29">29</A> See, for example: Witt A. Bergman J. J. Org. Chem. 2001, 66: 2784

<A NAME="RT09207SS-30">30</A> Gompper R. Breitschaft W. Angew. Chem., Int. Ed. Engl. 1983, 22: 717

<A NAME="RT09207SS-31">31</A> Caballero E. Avendaño C. Menéndez JC. Tetrahedron: Asymmetry 1998, 9: 967

<A NAME="RT09207SS-32">32</A> For a large-scale preparation of this compound see: Göshke R. Stutz F. Heinzelmann W. Maibaum J. Helv. Chim. Acta 2003, 86: 2848