Y-Lactone ring

The highest priority ring disconnective T-goals for 272 are those which disconnect a cocyclic 5,5-fusion bond and offexendo bond pair. The internal ketene-olefin cycloaddition in tactical combination with the Baeyer-Villiger transform is well suited to the double disconnection of such a cyclopentane-y-lactone ring pair. 

The y-lactone ring of the steroid skeleton forms an intermediate cardenohde anion in alkaline medium that nucleophilically adds to the 3,5-dinitrobenzoic acid in the position ortho to the two nitro groups. A mesomerically stabilized red-violet anion is produced (Meisenheimer complex). 

Reductive y-lactone ring opening, with concomitant desilylation at the tertiary position by LiAlH4, gave triol 17 in 80% yield. Finally, acetonide formation followed by oxidation with tetra-n-propylammonium perruthenate/A-methylmorpholine / /-oxide oxidation, led to the target aldehyde 19 in 80% overall yield. 

Both of them are accompanied by compounds where the C-teiminal Hse forms a y-lactone ring (azotobactin 87-11 and 8). An azotobactin O for which also a structure had been proposed (720) was shown later to be identical with azotobactin D (272). For secondary metabolites see protochelin and its constituents (Sect. 3.2). 

Acetals are acid sensitive but alkaline stable because their hydrolysis requires activation of the oxygen atom by protonation or coordination with a Lewis acid. An ingenious way of differentiating two 2-methoxytetrahydroluran moieties during a synthesis of bilobalide [91] is to treat the tetracyclic intermediate with potassium hydroxide. Expulsion of a methoxide ion is triggered by attack of the y-lactone ring five carbons away. 

A new synthesis of ( )-menthofuran (155) has been described which involves a three-step reaction sequence from the cyclohexanone (152) via direct C-alkylation with ethyl 2-iodopropionate to give (153) (Scheme 35). Hydrolysis of the diester (153) with hydrochloric acid afforded 3,6-dimethyl-2,4,5,6,7,7a-hexahydrobenzofuran-2-one (154). The final step in the sequence was the conversion of the a,/3-unsaturated y-lactone ring into the furan ring by reduction with lithium aluminum hydride and 2-propanol to afford (i)-menthofuran (155) in satisfactory yield (80JOC1517). 

The API etoposide contains a strained fnms-y-lactone ring that undergoes acid and base-catalyzed degradation. Under basic conditions, the degradation... 

Yasuda T, Sakakibara A (1981) Hydrogenolysis of protolignin in compression wood V. Isolation of two trimeric compounds with y-lactone ring. Holzforschung 35 183-187... 

The y-lactone ring in cardenolides has also been modified.Digitoxigenin (520) or isodigitoxigenin (521) were directly transformed into a mixture of isomeric lactams (523) by treatment with ammonia or methylamine. The lactol-amide intermediate (522) could be isolated when the reaction was performed at room temperature, and this was transformed to the lactam (523) by dilute acid. Gitoxigenin (524) reacted in an analogous way to afford the related lactams (525). From these experiments, it appears that the reaction with cardenolides gives... 

Five-membered heterocycles have been used as substitutes for the y-lactone ring of cardenolides. Thus, the 17 -(5 -isoxazolyl)- and 17)8-(3 -pyrazolyl)-cardenolides (526) and (527) have been prepared from 20-ethoxy-21-formyl-3 -acetoxy-17)8-pregna-5,14,20-triene (528) by reaction with hydroxylamine and hydrazine hydrate, respectively. The isomeric 14a,15a- and 14) ,15/S-epoxides (529) and (530) in both series were then obtained by peracid treatment or alkaline cyclization of the respective 14,15-bromohydrin. 

All of the compounds isolated from T. cinerariaefolium have inhibited root growth of Chinese cabbage seedlings [32]. This physiological activity seems to be attributed to the sesquiterpenoids with an a-methylene-y-lactone ring system. 

The spectral properties of himgravine (A, ax 218 mp, loge 4.0 v ax 1754, 1684 cm i) revealed the presence of an a,jS-unsaturated y-lactone ring. Catalytic hydrogenation afforded himbacine in good yield and therefore the structure of the alkaloid was XXII or XXIII (2). A clear decision in favor of the former was readily reached from a study of the NMR-spectrum (12). 

Further studies on the synthesis of psuedoguaianolides cf. Vol. 6, p. 90) have resulted in the total synthesis of the cytotoxic compounds ( )-damsin (447) (Scheme 43) and ( )-confertin (449) (Scheme 44). The realization that many sesqui-terpenoids containing a-methylene-y-lactone rings display important biological activity (cf. pp. 88 and 96) has prompted the development of several procedures... 

The final main group of structures is composed of spirobiflavonoids (442-447) spirobiflavonoids made up of two C15 units (448-449) phenolic spiro derivatives derived from C15 and C14 units (450) a C15 moiety of flavonoid origin and a Ci4-stilbene substructure linked via a y-lactone ring (attachment of the stilbene derivative to the carbocation intermediate of the oxidation of flavanone to flavanol, and subsequent rearrangement of this intermediate) (451-452) and a C15 moiety of flavonoid origin and a Cu-stilbene substructure linked via a y-laetone ring (453-455). 

A Cj5 moiety of flavonoid origin and a Ci4-stilbene substructure linked via a y-lactone ring... 

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