Lactone ring

Phenol condenses with phthahc anhydride in the presence of concentrated sulphuric acid or anhydrous zinc chloride to yield the colourless phenolphthalein as the main product. When dilute caustic alkah is added to an alcoholic solution of phenolphthalein, an intense red colouration is produced. The alkali opens the lactone ring in phenolphthalein and forms a salt at one phenolic group. The reaction may be represented in steps, with the formation of a h3q)othetical unstable Intermediate that changes to a coloured ion. The colour is probably due to resonance which places the negative charge on either of the two equivalent oxygen atoms. With excess of concentrated caustic alkali, the first red colour disappears this is due to the production of the carbinol and attendant salt formation, rendering resonance impossible. The various reactions may be represented as follows ... 

Analysis We must first open tlie lactone ring ... 

Analysis This is a y-lactone and we spent time considering possible strategies for these compounds in fi ames 334-348. First open the lactone ring. This gives us a compound with 1,4- 1,5- and 1,6-dioxygenation relationships. FU follow the 1,6 through. 

The 1,6-difunctional hydroxyketone given below contains an octyl chain at the keto group and two chiral centers at C-2 and C-3 (G. Magnusson, 1977). In the first step of the antithesis of this molecule it is best to disconnect the octyl chain and to transform the chiral residue into a cyclic synthon simultaneously. Since we know that ketones can be produced from add derivatives by alkylation (see p. 45ff,), an obvious precursor would be a seven-membered lactone ring, which is opened in synthesis by octyl anion at low temperature. The lactone in turn can be transformed into cis-2,3-dimethyicyclohexanone, which is available by FGI from (2,3-cis)-2,3-dimethylcyclohexanol. The latter can be separated from the commercial ds-trans mixture, e.g. by distillation or chromatography. 

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porTreatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

Many natural products are lactones and it is not unusual to find examples m which the ring size is rather large A few naturally occurring lactones are shown m Figure 19 8 The macrohde antibiotics of which erythromycin is one example are macrocychc (large ring) lactones The lactone ring of erythromycin is 14 membered... 

Structures in which one or more (but not all) rings of an aggregate are lactone rings are named by placing -carbolactone (denoting the —O—CO— bridge) after the names of the structures that... 

The term macroHde was introduced to denote the class of substances produced by Streptomjces species containing a macrocyclic lactone ring (27). 

Almost all actinomycins have the same chromophore, a planar phenoxa2inone dicarboxyUc acid called actinocin. In dactinomycin, the stmcture of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-aHo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes /V-methyl isoleucine instead of /V-methylvaline. The lactone ring is always present. 

The NMR experiments 55 are obtained from actinomycin D in order to check the amino acid sequence, to assign proton-proton and some carbon-proton connectivities, and to deduce informations concerning proton distances and the spatial structure of both cyclopentapeptide lactone rings. Conditions CDCI3, 10 mg per 0.3 ml, 25 °C, 500 MHz H), 125 MHz ( C). (a) HH COSY plot ... 

Amino-4,6-dimethyl-3-oxo-3//-phenoxazine-l,9-dicarboxylic acid also named actinocin is the chromophor of the red antineoplastic chromopeptide aetinomyein D (formula A). Two cyclopenta-peptide lactone rings (amino acids L-threonine, D-valine, L-proline, sarcosine, and 7V-methyl-L-valine) are attached to the carboxy carbons of actinocin by two amide bonds involving the amino groups of threonine. 

The highest priority ring disconnective T-goals for 272 are those which disconnect a cocyclic 5,5-fusion bond and offexendo bond pair. The internal ketene-olefin cycloaddition in tactical combination with the Baeyer-Villiger transform is well suited to the double disconnection of such a cyclopentane-y-lactone ring pair. 

Heteratisine, C22H33O5N, crystallises in prisms, has m.p. 262-7° (dec.), [a]f7° + 40° (MeOH), forms a hydrochloride, m.p. 265-270° (dec.), contains one methoxyl and one methylimino group, two active hydrogens and a lactone ring, opened by alkali and re-formed on acidification. In a later paper the same authors describe the isolation of benzoylheteratisine, C29H3,03N, m.p. 213-4°, [a]jf° + 73° (EtOH), which yields a hydrochloride, m.p. 218-221° (dec.), and is hydrolysed to benzoic acid and heteratisine the latter they suggest may not exist naturally in the plant but may be produced from benzoylheteratisine during extraction. 

Again reductive opening of the lactone ring can be achieved at the chloro lactone or a,j5-unsaturated keto lactone stages. ... 

Fluorinated lactone rings are al.so opened by fluoride ion to give alkoxides that can he trapped by electrophiles [280] (equation 62). 

Stereostructure and synthesis of aplyronine A (macrolide with 24-member lactone ring), an antitumor substance of marine origin 96YGK1077. 

An intramolecular variant of the Stille coupling is suitable for the construction of macrocycles. An example is the ring-closing step to form a 14-membered lactone ring 8 in a synthesis of zearalenone as reported by Stille et al. ... 

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