Lactone hydroxylactones

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 ... 

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]. 

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. 

It is not necessary to have an all-carbon ring to preserve the cis geometry of a double bond. Lactones (cyclic esters) and cyclic anhydrides are useful too. A double bond in a five- or six-member ed compound must have a cis configuration and compounds like these are readily made. Dehydration of this hydroxylactone can give only a cis double bond and ring-opening with a nucleophile (alcohol, hydroxide, amine) gives an open-chain compound also with a cis double bond. The next section starts with an anhydride example. 

Hydroxylactonizations (equations 97-99) involve the formation of a stable and, in general, stereo-chemically defined epoxide intermediate with peroxy acids. In an ensuing step these epoxides are cy-clized with acid catalysis under the participation of the carboxylic group. If steric reasons prohibit ring closure, as in equation (98), the diol acid (278) is formed instead of the hydroxy lactone (275).Equation (99) ° shows an example for the stereocontrol of the epoxidation step by an axially oriented carb-oxy group, which is then in an appropriate position to close the lactone ring (281). 

One of the most practical approaches among those described in Fig. (4) involves optical resolution of hydroxylactone rac-13, which is readily derived from acetoxy lactone rac-1, an intermediate of... 

Oxidation of secondary alcohols in a two-phase system (3, 243-244). Full details of the oxidation of hydroxylactones to ketolactones and of lactones to keto acids have been published.1... 

Substituted succinic anhydride 10, hydrogenated over platinum oxide in ethyl acetate, afford hydroxylactone 11. The prolonged reaction affords a mixture of lactone 12 and acid 13 ... 

This complex transform can be envisaged by assuming that one equivalent of 3-8 attacks the enol lactone carbonyl group to afford the hydroxylactone 4-2 (Scheme 4.4). This unstable intermediate actually comprises a hemiacetal of an enol lactone. The reaction medium is sufficiently basic to cause the underlying diketone (4-3) to undergo aldol cyclization to form cyclohexenone 4-4. 

Batmangherlich and Davidson developed an enantiodivergent route to both enantiomers of tert-butyl nonactate by way of the lactone 156, with C-6 obtained from the a-C of glutamic acid 155 (Scheme 22) (35). The hydroxylactone 156 was protected as its rm-butyldimethylsilyl ether, which... 

The hydrolysis of 97 in alkaline conditions, followed by acid treatment, allowed the intramolecular lactonization, affording the hydroxylactone 98. Barton-type deoxygenation of 98 yielded the expected (+)-dihydronepetalactone 99. 

The ring strain inherent in eight- and nine-membered lactones has been exploited in trans-lactonizations to form larger lactones. Thus, the treatment of the lactone (130) with a catalytic amount of acid led to its smooth conversion to the unstrained 12-membered hydroxylactone (131) (Equation (7)). This translactonization procedure, which could also be effected by base, was also used to prepare a 15-membered lactone from a nine-membered lactone <77JA7359>. 

A recently disclosed route to A -6,9-thia-PGI methyl ester (279) involved hydroxylation of the Corey lactone (2i) to give the hydroxylactone (276). Further transformations gave the benzoate (277) and henceforth the disulphide (278). Intramolecular addition of sulphenyl bromide followed by dehydro-... 

This enzyme-like reactivity enables the synthesis of highly complex molecules from substrates containing carboxylic acids, such as picrotoxinin derivatives which, when exposed to the same oxidizing conditions, yield lactone and hydroxylactone products (Scheme 38). 

Lactones from hydroxylactones Selective reduction—Oxasteroids s. 17, 135 OH H... 

Hydroxylactones from cyanoacetals Diols from lactones... 

Other lactones can also be used. a-Bromo-y-butyrolactone (2.26) was converted to hydroxylactone 2.27.1 jhe lactone ring was opened by potassium phthalimide to give 2.28 and removal of the phthalimido group gave 2-hydroxy-4-aminobutanoic acid (2.29). 

Sodium tetrahydridoborate sodium hydroxide Lactones from hydroxylactones Selective reduction... 

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