Sclerin

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

A variation of this reaction was used to synthesize sclerin (3), a natural product believed to be biosynthesized from a penta-/f-carbonyl precursor (equation II.2... 

The hexasubstituted benzenoid compound (145) is synthesized in one step by the condensation of 2 mol of the dienol silyl ether (146) with 1 mol of methyl orthoacetate and TiCU. The reaction is believed to proceed through the intermediate (147). Compound (147) can be considered as a potential 1,3,5-trielectrophile. The more reactive sites in (147) are at C-5 and at C-3 respectively. Condensation of (147) with a second mole of (146) gives therefore regioselectively the aromatic compound (145). By this method, the plant growth substance sclerin (148) can easily be prepared. 

Diesters.—A novel cycloaromatization reaction is used for the preparation of an aromatic diester, which is subsequently converted into the natural product sclerin (Scheme 29). Yields are reasonable and the method has been applied to orthoesters, anhydrides, and lactones. 

The addition of [l- C]acetate, [2- C]acetate, and [l- C]formate to cultures of Sclerotinia sclerotiorum provides radioactive sclerin (48) with labelling patterns which are difficult to reconcile with a straight-chain acetate-derived P-polyketo-ester intermediate methylated at activated methylene positions. It has beeh suggested, therefore, that the biosynthesis of sclerin (48) involves condensation of two acetate-derived chains (c/ Scheme 10), with C-methylation occurring at an unspecified stage in the biosynthetic sequence. In addition, it has been proposed that the same two precursor units could condense in alternative ways to produce the co-metabolites, (SO) and (51), of sclerin. 

It should be noted, however, that the experimental data do not exclude the intermediacy of a C-methylated straight-chain P-pentaketo-ester intermediate (52). Intramolecular cyclization of (52) and appropriate ring cleavage of the bicyclic intermediate (53) could also account for the formation of sclerin and one of its co-metabolites (49) (c/ Scheme 11). 

The incorporation of sclerotinin A (72) into sclerin (17) 21,106) provides an interesting example of a biosynthetic rearrangement (Scheme 8). 

Barber, J., M.J. Garson, and J. Stauton The Biosynthesis of Fungal Metabohtes Sclerin, a Plant Growth Hormone from Sclerotinia sclerotiorum. J. Chem. Soc. Perkin 1 1981, 2584... 

Garson, M.J., and J. Staunton Biosynthesis of Sclerin Incorporation Studies with Advanced Precursors. Chem. Commun. 1978, 158. 

Kubota, T., T. Tokoroyama, T. Kamikawa, and Y. Satomura Structures of Sclerin and Sclerolide, Metabolites of Sclerotinia libertiana. Tetrahedron Letters 1966, 5205. 

Satomura, Y., and A. Sato Isolation and Physiological Activity of Sclerin, a Metabolite of Sclerotinia Fungus. Agric. Biol. Chem. 29, 337 (1965). 

Sclerins, Seleroproteins, or Albuminoids.— Insoluble proteins found in the skeletal, connective, and epidermal tissues of animals. They do not occur in plants. Seleroproteins are very stable, and resist acid and alkaline hydrolysis, but ultimately are resolved into amino acids. 

These are consistent with formation of sclerin (27) via ring... 

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