Diolide

Sc(OTf)3, AcOH, p-nitrobenzoic anhydride or Sc(OTf)3, AC2O, 66- >95% yield. The lower yields are obtained with allylic alcohols propargylic alcohols give higher yields. Phenols are effectively acylated with this catalyst, but at a much slower rate than simple aliphatic alco-hols. The method was shown to be superior to most other methods for macrolactonization with minimum diolide formation. 

CO-Hydroxycarboxylic acids give, after silylation to bis(trimethylsilylated) intermediates and subsequent treatment with mild Lewis acdds, small- and large-ring lactones in high yields. Thus co-hydroxytridecanoic acid 332 (n= 12) affords, via 333 n= 12), at room temperature, the macrolide 334 in 89% yield [115]. The medium-sized 8- and 9-membered lactones are, however, not formed, only diolides. Likewise, trimethylsilyl 6-trimethylsilyloxyhexanoate 333 is readily lactonized in the presence of 4-trifluoro-... 

As indicated in the section describing the structures of natural dilactones, wentilactone B was wrongly assigned when the structure of 30-hydroxy-13,14,15,16-tetranorlabda-7,9(ll)-dien-(19,6(J),(12,17)-diolide was isolated. Our synthesis of this compound allows the reassignment of the structure of wentilactone B. Thus, the hydroxyl group of this natural podolactone should be relocated at C-2 with an a- configuration [87]. Two double cyclization steps were employed in this synthesis. The first involves the construction of the bicyclic skeleton via a Mn(III)-mediated... 

Macrolides. Nine- and ten-membered lactones cannot be obtained from treatment with Cs2C03 in DMF because of preferred inlcrmolecular cyclization (9, 100).2 However, the mesylate of 9-hydroxydecanoic acid is cyclized by Cs2C03 in DMF to phoracantholid 1 (1) in 45% yield together with I lie diolide (25% yield). Similar treatment of the mesylate of 10-hydroxydecanoic acid results in the lactone and the diolide in the ratio 7 3. Cyclization proceeds in very low yield when an a,/5-double bond is introduced.3... 

The reaction product consisted of 53% trans- and 38% r-2,6-di-methyl-2,4,6-octatriene-l,4 5,8-diolide and 9% of the 2,7-dimethyl analog. 

Lactonization. Heating the cesium salt of tu-bromo- or w-iodocarboxylic acids at 40° in DMF produces mixtures of lactones and diolides, ... 

The Mitsunobu procedure has found considerable application, so it has been used for diolide formation in pyrenophorin (equation 138) °° and colletodioF° syntheses. Yamaguchi s method is much infe-rior. As expected, the ring closure in equation (138) proceeds with inversion of configuration. In a... 

So far, enzymatic macrolactonizatiiHis are on a model stage yet. Sih has tested the enantio- and dia-stereo-selectivity in the diolide formation hrom racemic (395). With lipase, high enantiomer selection in favor of the iRJi)-096) has been observed, whereas the diastereoselection is disappointingly low (equation 140). ... 

Neoclerodan-16,15,20,19-diolides (41-43) which have been isolated from S. madrensis [69]. 

The first totai synthesis of the ichthyotoxic marine naturai product (-)-apiyoiide A was accomplished by Y. Stenstrom and co-workers. The compound has a 16-membered lactone ring, four (Z)-double bonds, as well as a stereogenic center. Numerous macroiactonization protocols were tested, but most of them gave the diolide (dimer) except for the Corey-Nicoiaou procedure. 

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