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1448 J.C.S. Perkin I Synthesis of Calythrone and Related Cyclopentene-I ,3-diones via Rearrangement of 4-Y Iidenebutenol ides By Nicholas G. Clemo, David R. Gedge, and Gerald Pattenden," Department of Chemistry, The University, Nottingham NG7 2RD Treatment of 4-ylidenebutenolides with sodium methoxide in methanol results in rearrangement to the correspond- ing cyclopentene-1,3-diones in high yield. The general method is applied in a synthesis of calythrone [(l) from (1 8)] from Calythrix tetragons, and the related cyclopentene-1,3-diones [(15) from (14) ;(25) from (24) ; (27) from (26) ; (33) from (32) ; and (37) from (36)]. Attempts to rearrange the butenolide (21) to natural lucidone (2b), from lindera lucida were unsuccessful, and instead led to the corresponding 4-oxo-unsaturated ester (23).The relevance of the facile rearrangement of 4-ylidenebutenolides to cyclopentene-I ,3-diones, to a possible bio- synthetic route is considered. CALYTHRONE(1),192 linderone and lucidone (2b) of the cyclopentanediones (1) and (2) it has been sug- are representative members of a unique group of natur- gested, involves ring contraction of appropriate acyl- ally occurring p-triketones derived from a cyclopentane- phloroglucinol derivatives as a key stage.4, Support'v8 for this comes from the observation that treatment of humulone (6) and the 1,4-quinone (8) with alkali leads to humulinic acid (7) and demethyldihydrolinderone (9) lo respectively. The 4-ylidenebutenolide ring system (10) is isomeric with the cyclopentane-l,3-dione system, and aromatic precursors have been shown to be obligatory inter- a; R = OMe mediates in the biosynthesis of several natural members b;R = H (41 (5) H02C I (61 (71 of this class of compound,ll e.g.patulin (11)and multi- colic acid (12) from polyketide-derived aromatic inter- mediates, and vulpinic acid (13) from phenylalanine via the terphenylquinone polyporic acid. The familial relationship between the 4-ylidenebutenolide and the 0 cyclopentane-l,3-dione ring systems led us to speculate I 0 that the former may be implicated in the biosynthesis of cyclopentane-l,3-diones from aromatic precursors. To M:: Ph Me0 ascertain the plausibility of this supposition we have 00 0 examined the isomerisation of several 4-ylidenebutenol- ides under basic conditions.In this paper we report the outcome of these investigations, and the development 1,3-dione ring. In comparison with natural P-triketones of a synthesis of natural calythrone (1) and related derived from cyclohexane-l,3-diones, e.g. angustione (3), compounds.12 xanthostemone (4), tasmanone (5), and humulone (6),596 t The P-triketones are drawn in the ketonic forms to illustrate they have a very limited occurrence.t The biosynthesis their similarity; they actually exist as mixtures of enolic forms. As a model, we first examined the isomerisation of the 2-ylidenebutenolide (14) ,13which is readily prepared by Wit tig condensation between dimethylmaleic anhydride and acetylmethylenetriphenylphosphoranein refluxing t01uene.l~ The stereochemistry of (14) followed from the chemical shift of the olefinic proton (T 4.44) in the lH n.m.r.spectrum, and comparison with data from our earlier studies.14 Treatment of the butenolide with hot methanolic sodium methoxide l5followed by acidification with hydrochloric acid, effected isomerisation in the anticipated sense leading to the known cyclopentenedione (15)l6 in 90% yield. Spectral data (see Experimental section) showed that the molecule exists in the exocyclic enol form shown in (16). We next turned to the synthesis of calythrone (1)from the butenolide (18). A Wittig condensation between dimethylmaleic anhydride and the phosphorane (17) in hot toluene led to a single isomer of the expected ylidenebutenolide, which by comparison of spectral data with (14) and other analogues was assigned the 2-stereochemistry (18).Treatment of the butenolide with hot methanolic sodium methoxide, in a similar manner to (14), led to calythrone (1) in 80% yield, which showed spectral data closely similar to those published for natural ca

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