Hydroxylactones

For the dihydroxylation of the achiral enyne 11, Corey and co-workers have used the AD-mix-a, and without isolation of the intermediate diol 12, obtained the hydroxylactone 13 which is formed through an intramolecular transesterification ... 

Hydroxylactonization of (—)-29 with hydrogen peroxide and formic acid gave the tricyclic compound 90, [a] +47.9° (ethanol). Reduction of 90 with lithium aluminum hydride, followed by acetylation, provided the triacetate 91, which was converted into the pentaacetates 92 and 93 by aceto-lysis. 0-Deacetylation of 92 and 93 gave 7 and 94, respectively The physical constants of all enantiomeric carba-sugars are listed in Table 1. 

The cyclic a-hydroxylactone, pantolactone, has been used extensively as a chiral auxiliary in D-A reactions.84 Reactions involving TiCl4 and SnCl4 occur through chelated TSs.85... 

Using water as the solvent enhanced the rate of the hetero-Diels-Alder reaction relative to the dimerization of cyclopentadiene. In addition, the reaction is much faster at a low pH, which implies that the reaction is acid catalyzed. The 5,5-fused system generated has been used in the total synthesis of several bioactive compounds, including the anti-HIV agent (—)-carbovir (Eq. 12.51)121 and the hydroxylactone moiety of mevinic acids (Eq. 12.52).122... 

MISCELLANEOUS BENZOHETEROCYCLES Partial reduction of lactone 166 (using for example diisobutylaluminum hydride in the cold) affords lactol 167. Condensation with nitromethane leads to the corresponding alkylated tetrahydrobenzopyran 170. The sequence probably starts by aldol reaction of the hydroxylactone form of the lactol (168) with nitrome thane to give the vinyl nitro intermediate 169 ... 

As with pyridazines, phthalazines, the other benzopyridazines, were also prepared most frequently through the condensation of hydrazines with carbonyl-containing compounds, typically phthalate derivatives. Recently, Napoletano and co-workers demonstrated the condensation of hydroxylactone 189 and hydrazine to afford phthalazones 190. After POCI3 chlorination, advanced intermediates for a novel series of PDE4 inhibitor I, phthalazines 191 were prepared <00BMC2235>. 

Fig. 2.128. HPLC-MS summed base peak mass chromatograms of total extracts of (a) T. weissflogii culture, (b) control, (c) faecal pellets immediately after grazing (48h) and (d) pellets after ageing in filtered seawater in the dark for 30 days. Peak identification a = phaeophorbide-a b = pyrophaeophorbide-a c = 132-chlorophyllone-a d = 132-epi-chlorophyllone-a (carotenoid) e + f = 132-hydroxyhlorophyll-a, 15 -hydroxylactone, chlorophyll-a g = chlorophyll-a g = chlorophyll-a epimer h = chlorophyll-a-like i = hydroxyphaeophytin-a + unknown i = hydroxyphaeophytin-a epimer j = phaeophytin-a j = phaeophytin-a epimer k = purpurin-18-phytyl ester 1 = pyrophaeophytin-a m = chlorine-a-like t = 132-oxopyrophaeophytin-a u = 132-oxopyrophaeophorbide a-24-methylcholesta-5,24(28)-dien-3/ -yl-ester SCE Sterol n = C272 d.b.a o = C27 2 d.b. +C28 2 d.b. p = C29 2 d.b. q = C27 1 d.b. r = C28 1 d.b. + C29 2 d.b. s = C29 2 d.b. Reprinted with permission from H. M. Talbot et al. [293], (ad.b = number of double bonds. = carotenoid.)...

Cyclohexenones 34 also undergo a highly diastereoselective dihydroxylation to give cii-diols 39 (Scheme 11).22 These diol amides are converted to hydroxylactones 40 by an acid-catalyzed process involving retro aldol-realdolization prior to transacylation. The enantiomers of hydroxylactones 40 are obtained from iodolactones 35 by iodide exchange with 2,2,6,6-tetramethylpiperidin-l-yloxy free radical (TEMPO) followed by reductive cleavage of the TEMPO derivative with Zn in ElOAc. The enantiomeric purity of the hydroxylactones prepared by either route is 95-98% ee. 

Use of RuOj/aq. Na(IO )/CCl to oxidise the secondary alcohol function in hydroxylactones gave ketolactones, while lactones gave ketocarboxylates [201-203], The former reaction is exemplified by 5-ejco-enrfo-dihydroxybicyclo[2.2.1] heptane-2-e (i(9carboxylic acid-y-lactone giving the 5-keto-6-endo product (Fig. 2.9). A number of other hydroxylactones were similarly oxidised, as were y- or 5-hydroxycarboxylates to ketocarboxylates [201]. 

Fluorine has also been introduced onto the E ring. For instance, both epimers of 20-fluorocamptothecin, where the fluorine atom replaces the 20-hydroxyl, have been prepared by total synthesis via stereoselective fluorination with DAST of the (K) and (S) a-hydroxylactone precursors (Figure 4.53). An asymmetric... 

The 14-membered ring lactone 3 was methylated to give a cisjirans mixture of 4 with a 13 1 ratio in favor of the cw-isomer73. Alkylation of the dianion of the hydroxylactone 5 gave 6 with a 9 1 selectivity74, which can be interpreted in terms of a chelation-controlled conformation such as 7. 

Garbe L-A, Tressl R (2004) Metabolism of deuterated t/jreo-dihydroxy fatty acids in Saccha-romyces cerevisiae Enantioselective formation and characterization of hydroxylactones and y-lactones. Helv Chim Acta 87 180... 

Lactone formation on treatment of uneatumted acids with pwox acids ib not confined to the field of fatty acid chemistry. Howell m l Taylor obtained a hydroxylactone, for instance, on adding perfoi nm acid to the indene derivative shown in Eq. 1 106). An epoxide < assumed to constitute the intermediate stage of this transformation. 

Ruthenium tetroxide readily converts secondary alcohols to the corresponding ketone, and primary alcohols to aldehydes and acids.288,294 It is particularly recommended for converting alcohols which are difficult to oxidize with other reagents, for example, the hydroxylactone (105a) in equation (112).325... 

An allylic halide has been used to give a better result than the corresponding allylic acetate (Scheme 8E.21) [134]. Notably, only 0.05 mol% of catalyst was sufficient to produce the enantiopure product in 96% yield. To achieve high enantioselectivity, the reactivity of the substrate had to be modulated by slow addition of the nucleophile, This deracemization strategy offers an efficient alternative method for the preparation of hydroxylactone, which has served as a synthetically useful building block for various natural product syntheses [135,136]. 

Five- and six-membered /3-hydroxylactones have been synthesized diastereo- and (g) enantio-selectively from a,/l-unsaturated esters bearing a ketone tethered as the ester R group, in an intramolecular reductive aldol reaction catalysed by chiral bisphosphine complexes of copper .133... 

Under the conditions of the Pfitzinger reaction secondary alcohols are capable of being oxidized to ketones and entering into condensation with isatins with the formation of derivatives of 4-quinolinecarboxylic acid. Thus, the product 50 was obtained with a yield of 81% from the hydroxylactone 49 and isatin 7 [25],... 

Not only acids but also a-hydroxylactones (y- and S-) when submitted to the system DIB-iodine underwent oxidative decarboxylation, accompanied by -fragmentation. This reaction took place under non-photochemical conditions in various solvents, at 20-58°C. The substrates - mainly sugar derivatives - eventually yielded, after a mechanistically interesting route, j8-iodo or a,/ -unsaturated compounds. An example follows [71] ... 

Alkyi-3 -dihydroxypentanoic acids chiral hydroxylactones.1 The acetal (2) of an aldehyde formed from (R)-l couples with l,3-bis(trimethylsilyloxy)-l-methoxy-1,3-butadiene (3), to give a single isomer (4). The chiral auxiliary is... 

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