Lactones reductions

The mechanism of ester (and lactone) reduction is similar to that of acid chloride reduction in that a hydride ion first adds to the carbonyl group, followed by elimination of alkoxide ion to yield an aldehyde. Further reduction of the aldehyde gives the primary alcohol. 

White et al. developed a stereospecific synthesis of Z-olefins, including isotretinoin [84]. Thus, isotretinoin was obtained by a Reformatsky reaction of p-cyclocitral with the C5 bromoester, followed by DIBAL-H lactone reduction, lactol ring opening, selective olefin bond formation with ethyl 4-diethoxyphosphoryl-3-methyl-2-butenoate and further saponification, Fig. (46). 

The synthesis of 11 -oxaprostaglandins from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou which are liberated by periodate oxidation and lactone reduction (S. Hanessian, 1979 G. Lourens, 1973). 

Reduction of ketopantoic acid to D-pantoic acid (0, (4) in Fig. 8). Agrobacterium sp. S-246 is a good source of ketopantoic acid reductase. The yield of D-pantoic acid reached 119 g/1 (molar yield, 90% optical purity, 98% e.e.) on incubation with washed cells of the bacterium [102]. From a practical point of view, ketopantoic acid reduction with Agrobacterium cells has several advantages over ketopantoyl lactone reduction with Candida (or Rhodotorula) cells. The former results in a higher product yield, molar conversion and optical purity of the product than the latter. It is necessary to maintain the substrate level at lower than 3% in the case of the ketopantolactone reduction, but not for the ketopantoic acid reduction. 

The efficient stereocontrol observed in the benzylic lactone hydro-genolyses described in the section on Lactonization/Benzylic Lactone Reduction prompted an investigation into methods for preparing analogous fused bicyclic lactones from enamides 89, 92, 94, and 96. The possible intermediacy of benzylic carbocation 123 in the triethylsilane... 

With the desired lactones 140, 134, 135, and 136 in hand, hydro-genolysis with a variety of heterogeneous catalysts was carried out following the general principles outlined in the section on Lactoniza-tion/Benzylic Lactone Reduction. The crude products containing acids 141 to 144 and their corresponding C-4 epimers 145 to 148 were... 

The 5-exo-trig radical cyclization resulted in exclusive formation of cw-annulated bicyclic compounds 29 and 34, which were in parallel transformed into cyclitols 30 and 35 by lactone reductive opening and deacetylation. In a divergent manner, by preserving the integrity of the... 

D-Gulonic acid, 2-amino-2-desoxy-, II, 62 —, 5-keto-, III, 147 —, 1,4-lactone, oxidation of, III, 147 —, 1,4-lactone, reduction of, IV, 216 D-Gulo-L-toZo-heptitoI, I, 11, 17 L-Gulonic acid, oxidation of, II, 85 L-Gulonic add, 6-desoxy-2-keto-, II, 87 —, 2,3 4,6-diisopropylidene-2-keto-, III, 164... 

D-Idonic acid, 2-amino-2-desoxy-, II, 62 D-Idonic lactone, reduction of, IV, 365 L-Idopyranose, 1,4-anhy dro-2,3,6-tri-methyl-, II, 69... 

Hydrolysis of ferrirhodin with HI gives serine, glycine, alanine, ornithine and ammonia in the ratio 0.20 1.00 1.55 2.95 0.02. Alanine is not found on hydrolysis with HC1. Periodate oxidation gives cfs-5-hydroxy-3-methyl-pent-2-enoic acid, isolated as the lactone. Reduction with H2 and palladium charcoal gives hexahydroferrirhodin, identical with hexahydroferrirubin. 

Capillary gas chromatographic determination of optical purities, investigation of the conversion of potential precursors, and characterization of enzymes catalyzing these reactions were applied to study the biogenesis of chiral volatiles in plants and microorganisms. Major pineapple constituents are present as mixtures of enantiomers. Reductions, chain elongation, and hydration were shown to be involved in the biosynthesis of hydroxy acid esters and lactones. Reduction of methyl ketones and subsequent enantioselective metabolization by Penicillium citrinum were studied as model reactions to rationalize ratios of enantiomers of secondary alcohols in natural systems. The formation of optically pure enantiomers of aliphatic secondary alcohols and hydroxy acid esters using oxidoreductases from baker s yeast was demonstrated. 

Lactones, reduction of with alkoxyaluminium hydrides 880R(36)249. 

Better results are obtained with ruthenium complexes of the corresponding thiono-lactones. Reductive ring cleavage with LiAlH4, then methylation and decomplexation, leads to the thioether (76 % ee). The chiral ruthenium complex recovered in this step can be converted back into the starting complex in two steps (Sch. 7) [55]. 

Crystalline L-altrose was described in 1934 by Austin and Humoller. After improving the methods for the preparation of L-ribose," they applied the cyanohydrin synthesis to 30 g. of that sugar and obtained 17 g. of crystalline calcium L-altronate and 14.5 g. of crystalline L-allono-7-lactone. Reduction of the latter with sodium amalgam yielded crystalline L-allose. The calcium L-altronate, by appropriate reactions, was converted to L-altrose, and the last of the sixteen theoretically possible aldohexoses had been prepared. Data on L-altrose and its derivatives are included in Table I. 

Koskinen and Otsomaa [92] have converted the L-threonine-derived aldehyde 131 (Scheme 13.50) into methyl 4-amino-4,6-dideoxy-gw/6>-pyranosides 134. A modified Homer-Wads worth-Emmons olefination leads to the (Z)-enoate 132. Acidic hydrolysis of the aminal protection affects lactonization giving 133. Double hydroxylation to the sterically less hindered face of the alkene moiety, followed by lactone reduction and methyl glycosidation furnishes 134 in 42% overall yield based on 131. 

Condensation of 2,3-O-isopropylidene-D-glyceraldehyde-A -benzylimine 211 with 2-(tri-methylsilyloxy)furan in the presence of a Lewis acid generates a mixture of butenolides 212 that is converted into D-nZ 6>-A, A -diprotected derivative 213 in 68% yield (Scheme 13.67) [119]. Dihydroxylation of 213, followed by diol protection and lactone reduction, furnishes the 5-amino-5-deoxyheptose derivative 214. Hydrogenolysis in MeOH generates 215 and its deprotection furnishes enantiomerically pure l,5-dideoxy-l,5-imino-D-g/yc r6>-D-a//6>-heptitol 216 [120]. 

Unusual carbanions. Lithium homoenolates are formed from P-aryl-a,P-unsaturated ketones and esters. Their reaction with carbonyl compounds leads to y-lactols and lactones. Reductive dechlorination of a-chloroimines provides a-amino carbanions. Access to 1,2-amino alcohols is assured. 

Lactols from lactones. Reduction of lactones by this reagent system at room... 

---