Lactols lactones

Common substructural motifs in polyketide natural products are six-membered ring lactones, lactols, and tetrahydropyrans. It was recognized by Wuts and co-workers that hydroformylation of readily available homoaUyhc alcohols would provide a direct and efficient entry into these ring systems. Such an approach was employed in a synthesis of Prelog-Djerassi lactone (Scheme 5.11) [13]. 

Formation of lactones, lactoles, muconic acids, and their derivatives by oxidative degradation of benzene rings 03T1105. 

Several of the oxygen-containing groups in Fig. 13.3 exhibit Bronsted acidity, namely carboxyl and phenohc hydroxyl groups. Carboxylic anhydrides and lactones are easily hydrolyzed to carboxylic anions, —COO , plus hydroxyl groups in the case of lactones. Lactols are in equilibrium with ketocarbonic acids a shown in the reaction scheme for 2-benzoylbenzoic acid (Reaction (13.1)) ... 

Thallium(iii) acetate with (130) gives the rearranged lactone (131), whose structure was established by AT-ray analysis lead tetra-acetate reacts in an analogous manner. The endo-epimer of (130) gives similar rearranged lactones. Lactol (132) in aqueous alkaline solution gives (133) with chlorine, and further transformations of (133) are noted. Previous attempts to prepare (134) by treatment of (135) with base have given mainly (136). By use of dimethylform-amide as solvent, conversion of (135) into (134) proceeds efficiently. Full... 

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

The slow oxidation of primary alcohols, particularly MeOH, is utilized for the oxidation of allylic or secondary alcohols with allyl methyl carbonate without forming carbonates of the alcohols to be oxidized. Allyl methyl carbonate (564) forms 7r-allylpalladium methoxide, then exchange of the methoxide with a secondary or allylic alcohol 563 present in the reaction medium takes place to form the 7r-allylpalladium alkoxide 565, which undergoes elimination of j3-hydrogen to give the ketone or aldehyde 566. The lactol 567 was oxidized selectively with diallyl carbonate to the lactone 568 without attacking the secondary alcohol in the synthesis of echinosporin[360]. 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

With the co side chain at C-12 in place, we are now in a position to address the elaboration of the side chain appended to C-8 and the completion of the syntheses. Treatment of lactone 19 with di-isobutylaluminum hydride (Dibal-H) accomplishes partial reduction of the C-6 lactone carbonyl and provides lactol 4. Wittig condensation8 of 4 with nonstabilized phosphorous ylide 5 proceeds smoothly and stereoselectively to give intermediate 20, the bistetra-hydropyranyl ether of ( )-1, in a yield of -80% from 18. The convergent coupling of compounds 4 and 5 is attended by the completely selective formation of the desired cis C5-C6 olefin. 

Cleavage of the imidazolidine moiety by acidic hydrolysis led to chiral lactols 17, which can be further oxidized to lactones 19 or reduced to diols 1848. 

Lactams 618 <5-Lactols 627 Lactones 617 reactions of 636 synthesis of 632, 737, 815 a,fl-unsaturated - see a,/J-Unsaturated lactones... 

---