Lactones contraction

One final comment on the biological activity of the sesquiterpene lactones in relation to ENE disease in horses. Unfortunately, horses are the only animal which contract this disease. Consequently, acquiring sufficient pure material to be fed to horses becomes a formidable task. At the present time, trial studies are being initiated with solstltlalln-A to observe its effect on horses. Insufficient material is available to permit the testing of the other sesquiterpene lactones. 

Selective silylation of aldohexono-1,4-lactones with tert-butylchlorodi-methylsilane gave the 2,6-di-O-silylated derivatives as major products (40). However, D-glucono-1,5-lactone underwent ring-contraction during silylation to give 2,6-di-O-terl-butyldimethylsilyl-D-glucono-1,4-lactone (31a) together with its 5,6-di-O-silyl isomer (31b), in 65 and 18% yields, respectively. 

The 2-trifluoromethanesuIfonates of the four diastereomeric 3,5-di-O-benzyl-pentono-1,4-lactones (such as D-ribono-1,4-lactone, 283) gave, upon treatment with potassium carbonate in methanol, the ring-contraction product, methyl oxetane-2-carboxylate (284). The stereochemistry at C-2 of the resulting oxetanes is determined by the configuration at C-3, rather than C-2, of the starting lactones (267). 

Methyl oxetane-2-carboxylate derivatives (e.g., 284), obtained by ring contraction of aldonolactones, have been employed for the synthesis (279) of the nucleoside / -noroxetanocin [9-(/ -D-eryt/iro-oxetanosyl)adenine, 304] and its a-anomer via an a-chloride obtained by a modified Hunsdiecker reaction. Displacement of chloride by adenine and debenzylation gave 304. The threo isomer of304, /J-epinoroxetanocin (305), was likewise synthesized from D-lyxono-1,4-lactone. The oxetane nucleosides display potent antiviral activity against the human immunodeficiency virus (HIV). 

Oxygen- and sulfur-assisted methods have been described to synthesize strained macrolactams by ring contraction through attack of the amine on the intermediate macro(thio)lactone [37]. 

Kricheldorf HR, Lee S-R, Schittenhehn N (1998) Macrocyclic polymerization of (thio) lactones - stepwise ring expansion contraction. Macromol Chem Phys 199 273-282... 

Ring contraction of readily available sugar derivatives has been used in synthetic approaches towards C-nucleosides, and the first ring contraction under acidic conditions of benzylated 2-bromo-2-deoxy-1,5-lactones to give... 

A wide range of acetal-protected aldono-1,5-lactones ready for preparing C-2 activated aldonolactones has been published [115] and used for preparation of highly functionalized tetrahydrofurans. The ring contractions were... 

Macrocyclic lactones. Ireland and Brown1 have adapted the Eschenmoser contraction of sulfides to a synthesis of five- and six-membered lactones. An example is formulated in equation (1). A hydroxy thioamide is esterified to give a chloro ester, which is then treated in sequence with Nal and phosphine I. The inelhod can also be used for preparation of macrocyclic lactones under high-dilution... 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

The cyanobromide (371) was condensed with the bc portion (347) to give the thioether (372) sulfide contraction to give (373) was accomplished using tris(/3-cyanoethyl) phosphine, and with phosphorus pentasulfide the thiolactam-thiolactone (374) was produced. After treatment with Meerwein s salt, reaction with dimethylamine opened the lactone with concomitant formation of an exocyclic methylene group, and subsequent treatment with cobalt chloride or iodide gave the chelate (375) which was reacted with diazabicyclononane to give bisnorcobyrinic add [Pg.435]

The enantiopure (A)-(+)-6-amino-l,3-oxazepan-4-one 29 was obtained in 35% yield by acid-catalyzed condensation of 28 (obtained in two steps from natural asparagine) with dimethoxypropane (Equation (3) see also Section 13.08.3.1). This reaction, which was very sensitive to both reaction conditions and the nature of the acid catalyst, was shown to proceed via the amide 30. Further reaction of 28 under forcing conditions (heating in toluene with />-toluenesulfonic acid) resulted in ring contraction to lactone 31 <1999H(51)365>. 

E is facile. Dehydrochlorination provides the aromatic products 233. An alternatively possible HC1 elimination/electrocyclization/decarboxylation pathway was excluded, since lactone 230B was thermally stable under the reaction conditions in the absence of the catalyst. (NHC)Cu(I) catalyst 232 gave comparable or better yields than 231 in these ATRC/ring contraction sequences, while other (NHC)Cu(I) complexes provided considerably lower yields [320]. Chlorinated cyclic compounds arising from ATRC can also be transformed to chlorinated furans [321]. 

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