Hydroxy-lactones => anhydrides

The photolysis of the 6-oxo-3a,5a-cyclo-19-oic acid (520) gives initially the 4-en-6-one (521), but in t-butanol a rapid photo-addition then affords the 4a-t-butoxy-6-hydroxy-lactone (522). Similar reactions transformed the methyl ester (523) into the ketonic derivative (525). Photolysis of the saturated keto-acid (526), in an alcohol as solvent, gave first the corresponding 6-monoester (527) of the 5,6-seco-6,19-dioic acid, and finally the 6,19-anhydride (528). Formation of the 6-ester (527) probably involves addition of the solvent alcohol to a keten intermediate. ... 

Lactone Anhydrides formed by intermolecular elimination of water between the hydroxyl and carboxyl groups of hydroxy acids. 

The hydrogenation of substituted succinic anhydrides such as 65, over platinum oxide at room temperature and 3-4 atmospheres leads to the initial formation of the hydroxy lactone, 66. Further hydrogenation in acetic acid at the same temperature and pressure converts 65 into a 2 1 ratio of the lactone, 67 and the methyl acid, 68. Extended hydrogenation of the anhydride in ethyl acetate gave almost equal amounts of 67 and 68 (Eqn. 18.42). Since anhydrides such as 65 are available from Diels-Alder reactions with maleic anhydride, this procedure has synthetic utility since the hydrogenations take place exclusively on the least hindered carbonyl group of the anhydride. 

The Chemistry of Rii% b.— The 9— 6p lactone (44, R = H) of the 12-methoxy-podocarpa-8,ll,13-triene series was obtained by the successive dehydration of the 7a- and 7)3-hydroxy-lactones with toluene-p-sulphonic acid in acetic anhydride and hydrogenation of the resulting A -enol-lactone over palladium-charcoal. Examination of the width of the C-6 proton resonance led to the... 

Upon treatment of the mixture of (278) and (279) with excess manganese dioxide in chloroform there was of hydroxy lactone (280), which was treated with excess lithium hexamethyldisilazane and sequential addition of chlorotrimethylsilane and A-bromosuccinimide provided ketone (281), and exposure of tetra-butylammonium fluoride provided treated with (R)-2-methylbutyric anhydride, DMAP to give to two diastereoisomers, which were deprotected providing two diastereomers (282) (simalikalactone D) and (283) which separated by HPLC. 

Basic catalysts other than alkali acetates have been employed in the Perkin reaction thus salicylaldehyde condenses with acetic anhydride in the presence of triethylamine to yield coumarin (tlie lactone of the cis form of o-hydroxy-cinnamio acid) together with some of the acetyl derivative of the trans form (o-acetoxycoumaric acid) ... 

The principles set forth above account reasonably well for the course of bifunctional condensations under ordinary conditions and for the relative difficulty of ring formation with units of less than five or more than seven members. They do not explain the formation of cyclic monomers from five-atom units to the total exclusion of linear polymers. Thus 7-hydroxy acids condense exclusively to lactones such as I, 7-amino acids give the lactams II, succinic acid yields the cyclic anhydride III, and ethylene carbonate and ethylene formal occur only in the cyclic forms IV and V. 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

Some of the versions of the mixed anhydride technique discussed may involve components other than a-hydroxy acids. Therefore, the resultant products cannot be considered as main-chain modified peptidomimetics. However, on many grounds these methods are of general importance in depsipeptide synthesis. For example the classical peptide reagent isobutyl chloroformate appears to be suitable for ester bond formation through the corresponding mixed anhydride with Boc- or Z-protected amino acids and the Thr (3-hydroxy group in the synthesis of a number of natural peptide lactones.145 7 ... 

In a situation where severe steric hindrance (e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both A17(20)-enol lactone acetates. Epoxidation with peracid, and mild alkaline hydrolysis proceeds to give the 17a-hydroxy-20-ketone in a high overall yield.257... 

The product of ozonolysis was acetylated in 6 ml of pyridine and 3 ml acetic anhydride at room temperature for 17 hours, 6 ml xylene was added and the reaction mixture evaporated in vacuo. The residue was triturated with ether-hexane affording crystalline (+/-)-2a-(2-acetoxy-2-carboxyvinyl)-3p-hydroxy-5-oxo-ip-cyclopentaneheptanoic acid methyl ester 6-lactone, 5-cyclic ethylene acetal, m.p. 82-84°C. 

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