A Novel Cyclisation Strategy for the Synthesis of Lactonamycin: A New Route to Highly Functionalised Heterocyclic Rings

Philip J. Parsons; Johnathan Board; Alexander J. Waters; Peter B. Hitchcock; Florian Wakenhut; Daryl S. Walter

doi:10.1055/s-2006-951542

LETTER

A Novel Cyclisation Strategy for the Synthesis of Lactonamycin: A New Route to Highly Functionalised Heterocyclic Rings

Philip J. Parsons*^a, Johnathan Board^a, Alexander J. Waters^a, Peter B. Hitchcock^a, Florian Wakenhut^b, Daryl S. Walter^c
^a Department of Chemistry, School of LifeSciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QJ, UK
Fax: +44(1273)678861; e-Mail: P.J.Parsons@sussex.ac.uk;
^b Pfizer Ltd., Ramsgate Road, Sandwich, Kent CT13 9MJ, UK
^c GlaxoSmithKline Research & Development Ltd., New Frontiers Science Park, Third avenue, Harlow, Essex CM19 5AW, UK

Abstract

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Abstract

A novel thermal cascade reaction equivalent to the well-known [2+2+2] cycloaddition has been developed which is clean and reliable and does not involve the use of metal ions. This highly efficient method has been used to construct a model for the synthesis of the antibiotic lactonamycin. The utility of this new sequence for the formation of furans is also reported.

Key words

lactonamycin - furan - cascade - cyclisation - thermal

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References and Notes

<A NAME="RD26606ST-1">1</A> Matsumoto N. Tsuchida T. Maruyama M. Sawa R. Kinoshita N. Homma Y. Takahashi Y. Iinuma H. Naganawa H. Sawa T. Hamada M. Takeuchi T. J. Antibiot. 1996, 49: 953

<A NAME="RD26606ST-2A">2a</A> Matsumoto N. Tsuchida T. Maruyama M. Kinoshita N. Homma Y. Iinuma H. Sawa T. Hamada M. Takeuchi T. Heida N. Yoshioka T. J. Antibiot. 1999, 52: 269

<A NAME="RD26606ST-2B">2b</A> Matsumoto N. Tsuchida T. Nakamura H. Sawa R. Takahashi Y. Naganawa H. Iinuma H. Sawa T. Takeuchi T. Shiro M. J. Antibiot. 1999, 52: 276

<A NAME="RD26606ST-3">3</A> Cox CD. Danishefsky SJ. Org. Lett. 2000, 2: 3493

<A NAME="RD26606ST-4">4</A> Cox CD. Danishefsky SJ. Org. Lett. 2001, 3: 2899

<A NAME="RD26606ST-5">5</A> Cox CD. Siu T. Danishefsky SJ. Angew. Chem. Int. Ed. 2003, 42: 5625

<A NAME="RD26606ST-6">6</A> Cox CD. Siu T. Danishefsky SJ. Angew. Chem. Int. Ed. 2003, 42: 5629

<A NAME="RD26606ST-7">7</A> Deville JP. Behar V. Org. Lett. 2002, 4: 1403

<A NAME="RD26606ST-8">8</A> Kelly TR. Xu D. Martinez G. Wang H. Org. Lett. 2002, 4: 1527

<A NAME="RD26606ST-9">9</A> Kelly TR. Cai XL. Tu B. Elliott EL. Grossmann G. Laurent P. Org. Lett. 2004, 6: 4953

<A NAME="RD26606ST-10">10</A> Henderson DA. Collier PN. Pave G. Rzepa P. White AJP. Burrows JN. Barrett AGM. J. Org. Chem. 2006, 71: 2434

<A NAME="RD26606ST-11">11</A> Parsons PJ. Penkett CS. Shell AJ. Chem. Rev. 1996, 96: 195

<A NAME="RD26606ST-12A">12a</A> Parsons PJ. Stefinovic M. Willis P. Meyer F. Synlett 1992, 864

<A NAME="RD26606ST-12B">12b</A> Henniges H. Meyer FE. Schick U. Funke F. Parsons PJ. de Meijere A. Tetrahedron 1996, 52: 11545

<A NAME="RD26606ST-12C">12c</A> Schweizer S. Sang ZZ. Meyer FE. Parsons PJ. de Meijere A. Angew. Chem. Int. Ed. 1999, 38: 1452

<A NAME="RD26606ST-13A">13a</A> Giese B. Kopping B. Chatgiliahoglu C. Tetrahedron Lett. 1989, 30: 681

<A NAME="RD26606ST-13B">13b</A> Kulieke KJ. Giese B. Synlett 1990, 91

<A NAME="RD26606ST-13C">13c</A> Dickhaut J. Giese B. Org. Synth., Coll. Vol. IX 1998, 738

<A NAME="RD26606ST-13D">13d</A> Parsons PJ. Penkett CS. Cramp MC. Warren ES. Tetrahedron 1996, 52: 647

<A NAME="RD26606ST-14">14</A> Lipshutz B. In Organometallics in Synthesis: A Manual Schlosser M. John Wiley and Sons Ltd.; Chichester: 1994. p.304

<A NAME="RD26606ST-15">15</A> Nudelman A. Bechor Y. Fabb E. Fischer B. Wexler BA. Nudelman A. Synth. Commun. 1998, 28: 471

<A NAME="RD26606ST-16">16</A> Nicolaou KC. Angew. Chem., Int. Ed. Engl. 1993, 32: 1377

<A NAME="RD26606ST-17A">17a</A> Corey EJ. Danheiser RL. Chandrasekaran S. Siret P. Keck GE. Gras J.-L. J. Am. Chem. Soc. 1978, 100: 8031

<A NAME="RD26606ST-17B">17b</A> Corey EJ. Danheiser RL. Chandrasekaran S. Keck GE. Gopalan B. Larsen SD. Siret P. Gras J.-L. J. Am. Chem. Soc. 1978, 100: 8034

A typical experimental procedure for the thermal cyclisation is shown below.
Synthesis of 6-Methyl-9-trimethylsilanyl-5,6,9,10-tetrahydrofuro[10,11- e ]isoindol-7-one(15). To 9-trimethylsilanyl-propynoic acid [4-(bromoallyl-oxy)but-2-ynyl]methyl amide (14, 0.342 g, 1.0 mmol) in toluene (10 mL) was added 1-epoxyhexene (1.00 g, 1.21 mL, 10.0 mmol). The solution was stirred at reflux for 1 h, after which time TLC showed the reaction to be complete. Toluene and 1-epoxyhexene were removed in vacuo and the product purified by column chromatography (Et₂O-hexane 7:3) to give the title compound as a bright yellow oil (0.235 g, 0.9 mmol, 90% yield). ¹H NMR (CDCl₃): δ = 7.31 (s, 1 H, C2), 7.14 (s, 1 H, C12), 4.15-4.24 (d, 1 H, J = 18.3 Hz, C5), 3.92-4.01 (m, 1 H, C5), 3.05 (s, 3 H, C13), 2.74-2.91 (m, 2 H, C9, C10), 2.32 (d, 1 H, J = 7.0 Hz, C10), -0.11 (s, 9 H, C14, C15, C16). ¹³C NMR (CDCl₃): δ = 173.6 (C7), 139.8 (C2), 138.3 (C4), 138.0 (C12), 137.1 (C8), 123.3 (C3), 121.4 (C11), 54.4 (C5), 32.0 (C13), 24.6 (C9), 21.9 (C10), 0.0 (C14, C15, C16). IR (neat): 3104, 2953, 2235, 1673, 1562, 851 cm^-1. MS (ES+): m/z = 284 [M + Na].

<A NAME="RD26606ST-19">19</A> Basak A. Mandel S. Bag SS. Chem. Rev. 2003, 103: 4077 ; and references cited therein

<A NAME="RD26606ST-20">20</A> This complements the cobalt-catalysed [2+2+2] cycloadditions reported by Vollhardt and others: Boese R. Harvey DF. Malaska MJ. Vollhardt KPC. J. Am. Chem. Soc. 1994, 116: 11153

<A NAME="RD26606ST-21">21</A> Urabe H. Nakajima R. Sato F. Org. Lett. 2000, 2: 3841